Brain creatine kinase activity in an animal model of mania

There is evidence pointing to dysfunction at the mitochondrial level as an important target for the understanding of the pathophysiology of bipolar disorder (BD). We assessed creatine kinase (CK) activity in rats submitted to an animal model of mania which included the use of lithium and valproate. In the acute treatment, amphetamine (AMPH) or saline was administered to rats for 14 days, and between day 8 and 14, rats were treated with either lithium, valproate or saline. In the maintenance treatment, rats were pretreated with lithium, valproate or saline, and between day 8 and 14, AMPH or saline were administered. In both experiments, locomotor activity was assessed by open-field test and CK activity was evaluated in hippocampus, striatum, cerebellum, whole cortex and prefrontal cortex. Our results showed that mood stabilizers reversed AMPH-induced behavioral effects. Moreover, AMPH (acute treatment) inhibited CK activity in hippocampus, striatum and cortex, but not in cerebellum and prefrontal cortex, and administration of lithium or valproate did not reverse the enzyme inhibition. In the maintenance treatment, AMPH decreased CK activity in saline-pretreated rats in hippocampus, striatum and cortex, but not in cerebellum and prefrontal cortex. AMPH administration in lithium- or valproate-pretreated animals decreased CK activity in hippocampus, striatum and cortex. Our results showed that AMPH inhibited CK activity and that mood stabilizers were not able to reverse and/or prevent the enzyme inhibition. These findings reinforce the hypothesis that mitochondrial dysfunction plays an important role in the pathophysiology of BD.     

Impaired pressure-induced constriction in mouse middle cerebral arteries of ASIC2 knockout mice

Recent studies from our laboratory demonstrated the importance of mechanosensitive epithelial Na(+) channel (ENaC) proteins in pressure-induced constriction in renal and cerebral arteries. ENaC proteins are closely related to acid-sensing ion channel 2 (ASIC2), a protein known to be required for normal mechanotransduction in certain sensory neurons. However, the role of the ASIC2 protein in pressure-induced constriction has never been addressed. The goal of the current study was to investigate the role of ASIC2 proteins in pressure-induced, or myogenic, constriction in the mouse middle cerebral arteries (MCAs) from ASIC2 wild-type (+/+), heterozygous (+/-), and null (-/-) mice. Constrictor responses to KCl (20-80 mM) and phenylephrine (10(-7)-10(-4) M) were not different among groups. However, vasoconstrictor responses to increases in intraluminal pressure (15-90 mmHg) were impaired in MCAs from ASIC2(-/-) and (+/-) mice. At 60 and 90 mmHg, MCAs from ASIC2(+/+) mice generated 13.7 +/- 2.1% and 15.8 +/- 2.0% tone and ASIC2(-/-) mice generated 7.4 +/- 2.8% and 12.5 +/- 2.4% tone, respectively. Surprisingly, MCAs from ASIC2(+/-) mice generated 1.2 +/- 2.2% and 3.9 +/- 1.8% tone at 60 and 90 mmHg. The reason underlying the total loss of myogenic tone in the ASIC2(+/-) is not clear, although the loss of mechanosensitive beta- and gamma-ENaC proteins may be a contributing factor. These results demonstrate that normal ASIC2 expression is required for normal pressure-induced constriction in the MCA. Furthermore, ASIC2 may be involved in establishing the basal level of myogenic tone.     

Infantile spasms is associated with deletion of the MAGI2 gene on chromosome 7q11.23-q21.11

Infantile spasms (IS) is the most severe and common form of epilepsy occurring in the first year of life. At least half of IS cases are idiopathic in origin, with others presumed to arise because of brain insult or malformation. Here, we identify a locus for IS by high-resolution mapping of 7q11.23-q21.1 interstitial deletions in patients. The breakpoints delineate a 500 kb interval within the MAGI2 gene (1.4 Mb in size) that is hemizygously disrupted in 15 of 16 participants with IS or childhood epilepsy, but remains intact in 11 of 12 participants with no seizure history. MAGI2 encodes the synaptic scaffolding protein membrane-associated guanylate kinase inverted-2 that interacts with Stargazin, a protein also associated with epilepsy in the stargazer mouse.     

Detection of <Emphasis Type="Italic">Diaphorina citri</Emphasis> Kuwayama (Hemiptera: Liviidae) in Kenya and potential implication for the spread of Huanglongbing disease in East Africa

The Asian citrus psyllid Diaphorina citri Kuwayama (Hemiptera: Liviidae) is a damaging pest of citrus globally and has recently been detected in Tanzania. Although direct damage by the pest is seldom of economic importance, the insect is more notorious for its ability to vector the fastidious phloem-limited bacterium Candidatus Liberibacter asiaticus (CLas), the putative causal bacterium of Huanglongbing or Asian citrus greening disease. For many years, Trioza erytreae (Del Guercio) (Hemiptera: Triozidae) was known to be the main vector of the African citrus greening disease caused by Candidatus Liberibacter africanus (CLaf), but the recent arrival of D. citri on the continent adds to the dynamics of infection and spread of both diseases on mainland Africa. Following the recent report of the presence of D. citri in Tanzania, an additional delimiting survey was carried out in the region, focusing on Kenya, mainland Tanzania and Zanzibar to detect the presence and ascertain the extent of spread of D. citri. We employed molecular tools based on the use of DNA barcoding to confirm the identity of D. citri. In addition to D. citri, the occurrence of T. erytreae in the same sampling locations is also reported. Adults and nymphs of either D. citri or T. erytreae were collected from citrus at many of the surveyed sites ranging from 19 to 668 m above sea level (masl) in Tanzania, 20–1666 masl in Kenya, and 42–48 masl in Zanzibar. Diaphorina citri was sympatric with T. erytreae at the mid to higher elevations of 1375–1666 masl and no T. erytreae or its open-gall symptoms were detected below 523 masl. Sequences obtained were queried via BLAST and all linked to D. citri of different accession numbers already available on GenBank. This is the first report of the presence of D. citri in Kenya and Zanzibar. The potential implication of the detection and spread of the two pathogens, CLaf and CLas to the citrus industry in East Africa and movement of suitable host plants is discussed.     

Stereoscopic correspondence for ambiguous targets is affected by elevation and fixation distance

Binocular correspondence must be determined if disparity is to be used to provide information about three-dimensional shape. The current study investigated whether knowledge of the statistical distribution of disparities in the natural environment is employed in this process. A simple model, which produces distributions of distances similar to those found in the natural environment, was used to predict the distribution of disparities in natural images. This model predicts that crossed disparities will be more likely as (i) stimulus elevation decreases below fixation and (ii) fixation distance increases. To determine whether these factors influence binocular correspondence for human observers, ambiguous stereograms were presented to observers, as stimulus elevation and fixation distance were manipulated. Clear biases were observed in the depth perceived in these stereograms, which were more likely to be seen as closer than fixation (i) for stimuli presented below fixation and (ii) as fixation distance increased. These results suggest that binocular correspondence is determined in a manner consistent with the distributions of disparities expected in natural scenes.     

Non-associative learning and anxiety in rats treated with a single systemic administration of the gastrin-releasing peptide receptor antagonist RC-3095

The gastrin-releasing peptide receptor (GRPR) has been implicated in the modulation of emotionally-motivated memory. In the present study, we investigated the role of the GRPR on non-emotional, non-associative memory, and anxiety. Adult male Wistar rats were given a systemic injection of the GRPR antagonist [D-Tpi⁶, Leu¹³ psi(CH₂NH)-Leu¹⁴] bombesin (6–14) (RC-3095) (0.2, 1.0 or 5.0 mg/kg) 30 min before exposure to an open field or an elevated plus maze. Habituation to the open field was tested in a retention trial carried out 24 h after the first exposure to the open field. Rats given RC-3095 at the doses of 1.0 or 5.0 mg/kg showed impaired habituation. Animals treated with 5.0 mg/kg of RC-3095 spent significantly more time in the closed arms of the elevated plus maze. No effects of RC-3095 on locomotion or exploratory behavior were observed. The results implicate the GRPR in the regulation of non-emotional, non-associative memory as well as in anxiety.