Local cerebral glucose utilization in the hippocampus of old rats

The local cerebral glucose utilization (LCGU) was measured in the different areas and layers of the Ammon's horn and dentate gyrus of young adult (3 to 4-month-old) rats, and of 27-month-old rats with proven cognitive deficits. The LCGU was determined by quantitative [14C]2-deoxyglucose autoradiography. Compared to young animals, in the old rats the LCGU was significantly reduced by 12% to 15% in the oriens layers of CA1 and CA2, the pyramidal layers of the CA sectors 1-3, the radiatum and lacunosum-molecular layers of CA2 and CA3 and in the lucidum layer of CA3. The LCGU values of all the other layers of the Ammon's horn and the dentate gyrus did not differ significantly between young and old rats. The pattern of the LCGU reduction found in the old rats roughly resembles changes found after fimbra-fornix lesions or systemic administration of scopolamine, suggesting a functionally important deficit in the cholinergic innervation of the old rats' hippocampi.     

Local cerebral glucose utilization in the Ammon's horn and dentate gyrus of the rat brain

The local cerebral glucose utilization (LCGU) was measured in different regions and layers of the Ammon's horn and dentate gyrus in the conscious rat. The LCGU was determined by quantitative [14C]2-deoxyglucose autoradiography using a computerized image processing system. In the hippocampus, the various regions and layers exhibited different glucose consumptions, the lowest values being found in the alveus and the highest ones in the lacunosum-molecular layers of the sectors of the Ammon's horn and the molecular layer of the dentate gyrus' external limb. Additionally, in many layers, the LCGU values of the left hemispheres were found to be higher compared with the right hemispheres. The analysis of LCGU changes in rostrocaudal direction revealed, that in sector 1 of Ammon's horn and in the dentate gyrus the glucose consumption decreased from rostral to caudal levels, whereas in sector 3 of Ammon's horn an increase was found.     

Local cerebral glucose utilization in the Ammon's horn and dentate gyrus of the rat brain

Summary The local cerebral glucose utilization (LCGU) was measured in different regions and layers of the Ammon's horn and dentate gyrus in the conscious rat. The LCGU was determined by quantitative [14C]2-deoxyglucose autoradiography using a computerized image processing system.In the hippocampus, the various regions and layers exhibited different glucose consumptions, the lowest values being found in the alveus and the highest ones in the lacunosum-molecular layers of the dentate gyrus' external limb. Additionally, in many layers, the LCGU values of the left hemispheres were found to be higher compared with the right hemispheres. The analysis of LCGU changes in rostrocaudal direction revealed, that in sector 1 of Ammon's horn and in the dentate gyrus the glucose consumption decreased from rostral to caudal levels, whereas in sector 3 of Ammon's horn an increase was found.Dedicated to Professor Dr. T.H. Schiebler on the occasion of his 65th birthday     

Local cerebral glucose utilization in the brain of old,learning impaired rats

Summary The local cerebral glucose utilization (LCGU) was measured in 63 different cortical areas and nuclei of the telencephalon, diencephalon and rhombencephalon of young adult (3 to 4-month-old) rats and of 27-month-old Wistar rats, in which learning impairments had been proven by a water maze test. The LCGU was determined by [¹⁴C]2-deoxyglucose autoradiography. In the old rats the mean LCGU of all brain regions was significantly reduced by about 10% compared with the young control group; the mean LCGU was 74.2 mol glucose/(100 g × min) in the young and 66.7 in the old rats. Different degrees of LCGU decrease were found in the different regions. Most of the brain regions with significantly reduced LCGU values in the aged, learning impaired rats were associated with auditory and visual functions, the dopaminergic system, and structures known to be involved in learning and memory processes. Therefore, the regional pattern of LCGU reduction found in the aged, learning impaired rats did not resemble any known pattern found after lesions of a single transmitter system or systemic administration of transmitter agonists or antagonists.     

Local cerebral glucose utilization in the brain of old, learning impaired rats

The local cerebral glucose utilization (LCGU) was measured in 63 different cortical areas and nuclei of the telencephalon, diencephalon and rhombencephalon of young adult (3 to 4-month-old) rats and of 27-month-old Wistar rats, in which learning impairments had been proven by a water maze test. The LCGU was determined by [14C]2-deoxyglucose autoradiography. In the old rats the mean LCGU of all brain regions was significantly reduced by about 10% compared with the young control group; the mean LCGU was 74.2 mumol glucose/(100 g x min) in the young and 66.7 in the old rats. Different degrees of LCGU decrease were found in the different regions. Most of the brain regions with significantly reduced LCGU values in the aged, learning impaired rats were associated with auditory and visual functions, the dopaminergic system, and structures known to be involved in learning and memory processes. Therefore, the regional pattern of LCGU reduction found in the aged, learning impaired rats did not resemble any known pattern found after lesions of a single transmitter system or systemic administration of transmitter agonists or antagonists.     

Developmentally regulated expression of brain-specific chondroitin sulfate proteoglycans, neurocan and phosphacan, in the postnatal rat hippocampus

Developmental changes in the distribution of brain-specific chondroitin sulfate proteoglycans, neurocan and phosphacan/RPTPzeta/beta, in the hippocampus of the Sprague-Dawley rat were examined using monoclonal antibodies 1G2 and 6B4. The 1G2 immunoreactivity was predominant in the neonatal hippocampus while the 6B4 immunoreactivity was predominant in the mature hippocampus. Moderate 1G2 immunoreactivity was detected in the dentate gyrus and subiculum immediately after birth. Immunoreactivity reached a peak on postnatal days 7-10 (P7-P10) when intense 1G2 labeling was present throughout the neuropil layers of the hippocampus except the mossy fiber tract. 6B4 immunoreactivity was limited in the stratum lacunosum moleculare of CA1 in the neonatal hippocampus. It gradually increased by P21 when diffuse 6B4 immunoreactivity was detected in the stratum oriens and radiatum of Ammon's horn, and in the hilus and inner one-third molecular layer of the dentate gyrus, while 1G2 immunoreactivity decreased after P21. In the adult hippocampus, moderate 6B4 immunoreactivity was present in the stratum oriens and radiatum of Ammon's horn, and in the hilus and inner one-third molecular layer of the dentate gyrus, but not in the mossy fiber tract. In addition, strong 6B4 labeling appeared around a subset of neurons after P21. The results suggest that neurocan may have a role in the development of neuronal organization, while phosphacan/RPTPzeta/beta may contribute to the maintenance and plasticity of synaptic structure and function. Furthermore, the absence of 1G2 and 6B4 immunoreactivities in the stratum lucidum suggests that neurocan and phosphacan/RPTPzeta/beta may function as a barrier for the extension of mossy fibers and provide an environment permissive for fasciculation of the mossy fibers.     

Electrophysiological and morphological characterization of dentate astrocytes in the hippocampus

We studied electrophysiological and morphological properties of astrocytes in the dentate gyrus of the rat hippocampus in slices. Intracellular application of Lucifer yellow revealed two types of morphology: one with a long process extruding from the cell body, and the other with numerous short processes surrounding the cell body. Their electrophysiological properties were either passive, that is, no detectable voltage-dependent conductance, or complex, with Na+/K+ currents similar to those reported in the Ammon's horn astrocytes. We did not find any morphological correlate to the types of electrophysiological profile or dye coupling. Chelation of cytoplasmic calcium ([Ca2+]i) by BAPTA increased the incidence of detecting a low Na+) conductance and transient outward K+ currents. However, an inwardly rectifying K+ current (Kir), a hallmark of differentiated CA1/3 astrocytes, was not a representative K+-current in the complex dentate astrocytes, suggesting that these astrocytes could retain an immature form of K-currents. Dentate astrocytes may possess a distinct current profile that is different from those in CA1/3 Ammon's horn.     

Localization of insulin-like growth factor-I mRNA in rat brain by in situ hybridization--relationship to IGF-I receptors

Recent evidence has demonstrated regional synthesis of insulin-like growth factor I (IGF-I) in rat brain, which is also known to contain widespread specific type I IGF receptors. In order to precisely define sites of IGF-I mRNA synthesis, and their relationship to IGF-I receptor sites, we have applied the techniques of in situ hybridization and in vitro receptor autoradiography in rat brain. Frozen sections of adult rat brain and liver were hybridized with 32P-labeled cDNA inserts for human IGF-I (780 base pairs) or a positive control transthyretin cDNA (1430 base pairs) probe, or a series of negative probes, followed by film or emulsion autoradiography. Receptor autoradiography was performed on similar sections using 125I-IGF-I in buffer, some chambers containing excess unlabeled IGF-I. Hybridization of IGF-I probe was clearly seen only in three major brain regions: the olfactory bulb, hippocampus and cerebellum, whereas transthyretin only hybridized to choroid plexus as expected, and other probes showed no hybridization. In olfactory bulb, hybridization was greatest in the internal granular and mitral cell layers, with lower levels in the glomerular layer, where IGF-I receptors were concentrated. In hippocampus, hybridization was to pyramidal cells of Ammon's horn in CA1 and CA2 layers and dentate gyrus, with some labeling in CA3. IGF-I receptors were most dense in CA2, CA3, CA4, and dentate gyrus. In cerebellum, hybridization was to the granule cell layer, with IGF-I receptors primarily in the adjacent molecular layer. We have clearly demonstrated precise sites of local IGF-I synthesis in adult rat brain, adjacent to, and sometimes overlapping sites of high density IGF-I receptors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Localization of type I insulin-like growth factor receptor messenger RNA in the adult rat brain by in situ hybridization.

Using multiple 35S-labeled oligonucleotide probes concurrently, the type I insulin-like growth factor receptor (IGF-I-R) mRNA was demonstrated by Northern blot hybridization in newborn and adult rat brain as a single species of approximately 11 kilobases. The probes were used to localize IGF-I-R mRNA by in situ hybridization in slices of adult rat brain. The highest levels of IGF-I-R mRNA expression were found in the glomerular and mitral cell body layers of the olfactory bulb, the granule cell body layers of the dentate gyrus and cerebellum, the pyramidal cell body layers of the piriform cortex and Ammon's horn, and the choroid plexus. The lowest levels of IGF-I-R mRNA expression were found in white matter. At the cellular level, IGF-I-R mRNA was expressed by a variety of neurons, by epithelial cells of the choroid plexus, and by ependymal cells of the third ventricle. Of the neuron types studied, the highest levels of IGF-I-R mRNA were consistently found in perikarya of mitral and tufted cells in the olfactory bulb, in pyramidal cells of the piriform cortex and Ammon's horn, and in granule cells of the dentate gyrus. There was a close congruency between the distribution of IGF-I binding and IGF-I-R mRNA at the regional level. Neuropil layers in the cerebral cortex, olfactory bulb, hippocampus, and cerebellum contained a high level of IGF-I binding, whereas the adjacent cell body layers contained a high level of the IGF-I-R mRNA. We conclude that in these regions, IGF-I-R mRNA is synthesized in neuronal cell bodies, and the receptors are transported to axons and dendrites in adjacent synapse-rich layers, where appropriate IGF effects are achieved.     

Inositol 1,4,5-Trisphosphate 3-Kinase mRNA: High Levels in the Rat Hippocampal CA1 Pyramidal and Dentate Gyrus Granule Cells and in Cerebellar Purkinje Cells

The distribution of inositol 1,4,5-trisphosphate (InsP3) 3-kinase mRNA in the rat brain is reported using oligonucleotides based on a cDNA clone sequence that encodes rat brain InsP3 3-kinase and the in situ hybridization technique. Moderate levels were found in CA2-4 pyramidal neurons, in the cortex, and in the striatum. The cerebellar granule cells, thalamus, hypothalamus, brainstem, spinal cord, and white matter tracts were almost negative. The levels of InsP3 3-kinase mRNA were highest in the hippocampal CA1 pyramidal neurons, granule cells of the dentate gyrus, and cerebellar Purkinje cells. These results contrast with the lower concentration of the InsP3 receptor already reported in the hippocampus versus the Purkinje cells and suggest a special role for inositol 1,3,4,5-tetrakisphosphate in Ammon's horn.     

Weakened Intracellular Zn<Superscript>2+</Superscript>-Buffering in the Aged Dentate Gyrus and Its Involvement in Erasure of Maintained LTP

Memory is lost by the increased influx of extracellular Zn²⁺ into neurons. It is possible that intracellular Zn²⁺ dynamics is modified even at non-zincergic medial perforant pathway-dentate granule cell synapses along with aging and that vulnerability to the modification is linked to age-related cognitive decline. To examine these possibilities, vulnerability of long-term potentiation (LTP) maintenance, which underlies memory retention, to modification of synaptic Zn²⁺ dynamics was compared between young and aged rats. The influx of extracellular Zn²⁺ into dentate granule cells was increased in aged rats after injection of high K⁺ into the dentate gyrus, but not in young rats. This increase impaired maintained LTP in aged rats. However, the impairment was rescued by co-injection of CaEDTA, an extracellular Zn²⁺ chelator, or CNQX, an AMPA receptor antagonist, which suppressed the Zn²⁺ influx. Maintained LTP was also impaired in aged rats after injection of ZnAF-2DA into the dentate gyrus that chelates intracellular Zn²⁺, but not in young rats. Interestingly, the capacity of chelating intracellular Zn²⁺ with intracellular ZnAF-2 was almost lost in the aged dentate gyrus 2 h after injection of ZnAF-2DA into the dentate gyrus, suggesting that intracellular Zn²⁺-buffering is weakened in the aged dentate gyrus, compared to the young dentate gyrus. In the dentate gyrus of aged rats, maintained LTP is more vulnerable to modification of intracellular Zn²⁺ dynamics than in young rats, probably due to weakened intracellular Zn²⁺-buffering.     

Immunoreactivities and Levels of Mineralocorticoid and Glucocorticoid Receptors in the Hippocampal CA1 Region and Dentate Gyrus of Adult and Aged Dogs

Corticosteroids are important factors in the maintenance of homeostasis in the brain. They are regulated via the interaction with two corticosteroid receptor systems—the mineralocorticoid (MR) and glucocorticoid receptor (GR). In the present study, we observed age-related changes in serum cortisol levels, and immunoreactivities and protein levels of MR and GR in the hippocampal CA1 region and dentate gyrus. The serum cortisol levels were significantly high (about twofold) in the aged group compared to that in the adult group. In the adult dog (2–3 years old), MR and GR immunoreactivity was detected in neurons in the pyramidal layer of the CA1 region, and in the granular and multiform layers of the dentate gyrus. In the aged dog (10–12 years old), MR immunoreactivity in the CA1 region was significantly decreased, especially, in the dentate multiform layer. In contrast, GR immunoreactivity in the aged dog was slightly decreased in the CA1 region and dentate gyrus. In the Western blot analysis, MR protein level in the aged dog was significantly lower compared to that of the adult dog; GR protein level in the aged dog was not significantly decreased. This result indicates that the reduction of MR immunoreactivity and protein level in the hippocampus of the aged dog may be associated with neural dysfunction in the aged hippocampus.     

Two Peptidergic Drugs Increase the Synaptophysin Immunoreactivity in Brains of 24-month-old Rats

The brain-derived peptidergic drug Cerebrolysin has been found to support the survival of neurones in vitro and in vivo. Positive effects on learning and memory have been demonstrated in various animal models and also in clinical trails. In the present study, the effects of Cerebrolysin and its peptide preparation E021 on the synapse density in the hippocampus, the dentate gyrus and in the entorhinal cortex of 24-month-old rats were investigated. Rats received the drugs or saline for control for 19 consecutive days (2.5ml/kg per day). Slices of the brains were immunohistochemically stained with anti-synaptophysin, which is a specific marker of presynaptic terminals. Quantification of the synapse density was done by using light microscopy and a computerised image analysing system. Our results clearly showed that the rats benefit from the administration of both drugs, showing an enhancement in the number of synaptophysin-immunostained presynaptic terminals in the entorhinal cortex, the dentate gyrus, and also in the hippocampal subfields CA1, CA2, CA3 stratum lucidum and CA3 stratum radiatum. It can be assumed that these effects are the reason for improved cognitive performances of rats treated with Cerebrolysin and E021.     

Surface L‐type Ca2+ channel expression levels are increased in aged hippocampus

Age‐related increase in L‐type Ca²⁺ channel (LTCC) expression in hippocampal pyramidal neurons has been hypothesized to underlie the increased Ca²⁺ influx and subsequent reduced intrinsic neuronal excitability of these neurons that lead to age‐related cognitive deficits. Here, using specific antibodies against Ca_v1.2 and Ca_v1.3 subunits of LTCCs, we systematically re‐examined the expression of these proteins in the hippocampus from young (3 to 4 month old) and aged (30 to 32 month old) F344xBN rats. Western blot analysis of the total expression levels revealed significant reductions in both Ca_v1.2 and Ca_v1.3 subunits from all three major hippocampal regions of aged rats. Despite the decreases in total expression levels, surface biotinylation experiments revealed significantly higher proportion of expression on the plasma membrane of Ca_v1.2 in the CA1 and CA3 regions and of Ca_v1.3 in the CA3 region from aged rats. Furthermore, the surface biotinylation results were supported by immunohistochemical analysis that revealed significant increases in Ca_v1.2 immunoreactivity in the CA1 and CA3 regions of aged hippocampal pyramidal neurons. In addition, we found a significant increase in the level of phosphorylated Ca_v1.2 on the plasma membrane in the dentate gyrus of aged rats. Taken together, our present findings strongly suggest that age‐related cognitive deficits cannot be attributed to a global change in L‐type channel expression nor to the level of phosphorylation of Ca_v1.2 on the plasma membrane of hippocampal neurons. Rather, increased expression and density of LTCCs on the plasma membrane may underlie the age‐related increase in L‐type Ca²⁺ channel activity in CA1 pyramidal neurons.     

Excitatory and Inhibitory Effects of A1 and A2A Adenosine Receptor Activation on the Electrically Evoked [3H]Acetylcholine Release from Different Areas of the Rat Hippocampus

Abstract: The modulation by adenosine analogues and endogenous adenosine of the electrically evoked release of [³H]acetylcholine ([³H]ACh) was compared in subslices of the three areas of the rat hippocampus (CA1, CA3, and dentate gyrus). The mixed A₁/A₂ agonist 2-chloroadenosine (CADO; 2–10 µM) inhibited, in a concentration-dependent manner, the release of [³H]ACh from the three hippocampal areas, being more potent in the CA1 and CA3 areas than in the dentate gyrus. The inhibitory effect of CADO (5 µM) on [³H]ACh release was prevented by the A₁ antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 50 nM) in the three hippocampal areas and was converted in an excitatory effect in the CA3 and dentate gyrus areas. The A_2A agonist CGS-21680 (30 nM) produced a greater increase of the evoked release of [³H]ACh in the CA3 than in the dentate gyrus areas, whereas no consistent effect was found in the CA1 area or in the whole hippocampal slice. The excitatory effect of CGS-21680 (30 nM) in the CA3 area was prevented by the adenosine receptor antagonist 3,7-dimethyl-1-propargylxanthine (10 µM). Both adenosine deaminase (2 U/ml) and DPCPX (250 nM) increased the evoked release of [³H]ACh in the CA1 and CA3 areas but not in the dentate gyrus. The amplitude of the effect of DPCPX and adenosine deaminase was similar in the CA1 area, but in the CA3 area DPCPX produced a greater effect than adenosine deaminase. It is concluded that the electrically evoked release of [³H]ACh in the three areas of the rat hippocampus can be differentially modulated by adenosine. In the CA1 area, only A₁ inhibitory receptors modulate ACh release, whereas in the CA3 area, both A_2A excitatory and A₁ inhibitory adenosine receptors modulate ACh release. In the dentate gyrus, both A₁ inhibitory and A_2A excitatory adenosine receptors are present, but endogenous adenosine does not activate them.     

人参皂甙对老龄大鼠海马结构BDNF及Trk B蛋白表达的影响

目的探讨老龄大鼠海马结构BDNF及Trk B蛋白表达的老龄性变化,同时对比观察人参皂甙对其改变的影响。方法雌性Wistar大鼠39只,分为青年组、老龄组、给药组(第17个月始饲以人参皂甙至27月龄)。采用免疫组化及Western blot方法对海马结构BDNF反应产物及Trk B蛋白进行定性、定量分析。结果老龄组CA3、CA1区BDNF含量分别较青年组下降13.3%、10.4%(P<0.05);其给药组和老龄组相比变化不大(P>0.05)。齿状回从青年到老年变化不明显(P>0.05),但给药组比老龄组增加16.7%(P<0.01)。老龄组海马结构Trk B蛋白表达较青年组下调了99.7%;给药组较老龄组上调了78.5%(P<0.01)。结论老龄组海马结构BDNF及Trk B蛋白表达较青年组明显降低,而人参皂甙可明显上调齿状回BDNF含量和海马结构Trk B蛋白的表达。     

双侧颈总动脉结扎对大鼠学习记忆相关脑区血流量的影响

目的为建立双侧颈总动脉结扎致大鼠血管性痴呆模型,观察了大鼠双侧颈总动脉结扎后不同脑区脑血流量的影响。方法采用激光多普勒血流仪,测定麻醉大鼠双侧颈总动脉结扎后１０ｍｉｎ内不同脑区脑血流量变化。结果大鼠双侧颈总动脉结扎后,平均脑血流量减少额区６７８３％、顶区５６８２％、枕区１６１６％、Ｍｙｎｅｒｔ基底核５１２１％、尾壳核４１１８％,海马ＣＡ１５１８３和海马ＣＡ２４１２１。结论大鼠双侧颈总动脉结扎后与学习记忆有关的脑区脑血流量均显著下降     

Neuroprotective action of FK-506 (tacrolimus) after seizures induced with pilocarpine: quantitative and topographic elemental analysis of brain tissue

In the present work, X-ray fluorescence microscopy with a synchrotron source for the exciting radiation was applied for topographic and quantitative elemental analysis of rat brain tissue in pilocarpine-induced epilepsy and neuroprotection with FK-506. The mass per unit area of the elements P, S, Cl, K, Ca, Fe, Cu, Zn, Se, Br, and Rb was determined in four fields of the hippocampal formation (sectors 1 and 3 of Ammon’s horn–CA1, CA3; dentate gyrus; hilus of dentate gyrus) and the parietal cortex. The results obtained for epileptic rats treated with FK-506 (SNF) were compared with data obtained previously for epileptic rats (SNS) and a control group. Many statistically significant differences in elemental composition were observed between the SNF and SNS groups. Higher mass per unit area of P was noticed in CA1 and CA3 regions of the hippocampus of SNF rats in comparison with SNS rats. A similar relation was observed for K in all five brain areas analyzed. Also, Fe in CA3 and dentate gyrus, Cu in the parietal cortex, and Zn in CA3 and in the cortex were present at a higher level in the SNF group in comparison with the SNS group. The findings obtained in the present study suggest that the neuroprotective action of FK-506 in epileptic rat brain may involve not only the inhibition of calcineurin but also blockade of the K⁺ channels.     

Cannabinoid receptor and WIN-55,212-2-stimulated [S]GTPγS binding and cannabinoid receptor mRNA levels in several brain structures of adult male rats chronically exposed to R-methanandamide

We and others have recently demonstrated that the pharmacological tolerance observed after prolonged exposure to plant and synthetic cannabinoids in adult individuals seems to have a pharmacodynamic basis, based on the observed down-regulation of cannabinoid receptors in the brain of cannabinoid-tolerant rats. However, we were unable to elicit a similar receptor down-regulation after a chronic exposure to anandamide, the first discovered endogenous cannabinoid, possibly because of its rapid metabolic breakdown in arachidonic acid and ethanolamine. The present study was designed to progress in these previous studies, by using R-methanandamide, a more stable analog, instead anandamide. In addition, we examined not only cannabinoid receptor binding, but also WIN-55,212-2-stimulated [³⁵S]-GTPγS binding, by autoradiography, and cannabinoid receptor mRNA levels, by in situ hybridization. Results were as follows. The daily administration of R-methanandamide for a period of five days produced decreases in cannabinoid receptor binding in the lateral caudate-putamen, cerebellum, entopeduncular nucleus and substantia nigra. The remaining areas, the medial caudate-putamen, globus pallidus, cerebral cortex (layers I and VI), hippocampus (dentate gyrus and Ammon’s horn) and several limbic structures (nucleus accumbens, septum nuclei and basolateral amygdaloid nucleus), exhibited no changes in cannabinoid receptor binding. Similarly, the levels of cannabinoid receptor mRNA expression decreased in the lateral and medial caudate-putamen and in the CA1 and CA2 subfields of the Ammon’s horn in the hippocampus after the chronic exposure to R-methanandamide, whereas the remaining areas showed no changes. WIN-55,212-2-stimulated [³⁵S]-GTPγS binding did not change in the lateral caudate-putamen, cerebral cortex (layer I), septum nuclei and hippocampal structures (dentate gyrus and Ammon’s horn) of animals chronically exposed to R-methanandamide, whereas a certain trend to decrease could be observed in the substantia nigra and deep layer (VI) of the cerebral cortex in these animals. In summary, as reported for other cannabinoid receptor agonists, the prolonged exposure of rats to R-methanandamide, a more stable analog of anandamide, was able to produce cannabinoid receptor-related changes in contrast with the absence of changes observed early with the metabolically labile anandamide. The observed changes exhibited an evident regional pattern with areas, such as basal ganglia, cerebellum and hippocampus, responding to chronic R-methanandamide treatment while regions, such as the cerebral cortex and limbic nuclei, not responding.     

Differential effects of treadmill exercise in early and chronic diabetic stages on parvalbumin immunoreactivity in the hippocampus of a rat model of type 2 diabetes

In the present study, we investigated the effects of treadmill exercise in early and chronic diabetic stages on parvalbumin (PV) immunoreactivity in the subgranular zone of the dentate gyrus of Zucker diabetic fatty (ZDF) and its lean control rats (ZLC). To investigate the effects, ZLC and ZDF rats at 6 or 23 weeks of age were put on a treadmill with or without running for 1 h/day/5 consecutive days at 16–22 m/min for 5 weeks or 12–16 m/min for 7 weeks, respectively. Physical exercise in pre-diabetic rats prevented onset of diabetes, while exercise in rats at chronic diabetic stage significantly reduced blood glucose levels. In addition, physical exercise in the pre-diabetic rats significantly increased PV immunoreactive fibers in the strata oriens and radiatum of the CA1-3 region and in the polymorphic and molecular layers of the dentate gyrus compared to that in sedentary controls. However, in rats at chronic stages, PV immunoreactivity was slightly increased in the CA1-3 region as well as in the dentate gyrus compared to that in the sedentary controls. These results suggest that physical exercise has differential effects on blood glucose levels and PV immunoreactivity according to diabetic stages. Early exercise improves diabetic phenotype and PV immunoreactive fibers in the rat hippocampus.