Association of limbic system-associated membrane protein (LSAMP) to male completed suicide

<p>Abstract</p> <p>Background</p> <p>Neuroimaging studies have demonstrated volumetric abnormalities in limbic structures of suicide victims. The morphological changes might be caused by some inherited neurodevelopmental defect, such as failure to form proper axonal connections due to genetically determined dysfunction of neurite guidance molecules. Limbic system-associated membrane protein (LSAMP) is a neuronal adhesive molecule, preferentially expressed in developing limbic system neuronal dendrites and somata. Some evidence for the association between LSAMP gene and behavior has come from both animal as well as human studies but further investigation is required. In current study, polymorphic loci in human LSAMP gene were examined in order to reveal any associations between genetic variation in <it>LSAMP </it>and suicidal behaviour.</p> <p>Methods</p> <p>DNA was obtained from 288 male suicide victims and 327 healthy male volunteers. Thirty SNPs from LSAMP gene and adjacent region were selected by Tagger algorithm implemented in Haploview 3.32. Genotyping was performed using the SNPlex™ (Applied Biosystems) platform. Data was analyzed by Genemapper 3.7, Haploview 3.32 and SPSS 13.0.</p> <p>Results</p> <p>Chi square test revealed four allelic variants (rs2918215, rs2918213, rs9874470 and rs4821129) located in the intronic region of the gene to be associated with suicide, major alleles being overrepresented in suicide group. However, the associations did not survive multiple correction test. Defining the haplotype blocks using confidence interval algorithm implemented in Haploview 3.32, we failed to detect any associated haplotypes.</p> <p>Conclusion</p> <p>Despite a considerable amount of investigation on the nature of suicidal behaviour, its aetiology and pathogenesis remain unknown. This study examined the variability in LSAMP gene in relation to completed suicide. Our results indicate that LSAMP might play a role in pathoaetiology of suicidal behaviour but further studies are needed to understand its exact contribution.</p

A screen for genes induced in the amygdaloid area during cat odor Exposure

Behavior Genetics Association 33rd Annual Meeting Abstract

Rats with low exploratory activity in the elevated plus-maze have the increased expression of limbic system-associated membrane protein gene in the periaqueductal grey

The aim of a present study was to analyse the gene expression profiles in the periaqueductal grey (PAG) of rats related to their exploratory activity in the elevated plus-maze model of anxiety. Animals were divided into the groups according to their exploratory activity in the plus-maze as follows: rats with low activity (‘anxious’), moderate activity (‘intermediate’) and high activity (‘non-anxious’). Control animals were not exposed to the elevated plus-maze. The differential expression of genes was analysed using the cDNA representational difference analysis (RDA) in combination with the sequencing and database search. Reverse transcription-polymerase chain reaction with specific primers was applied to confirm the differences found by the RDA. We established that animals displaying the different exploratory activity have also the different gene expression profiles in the PAG. Among the identified genes, we were able to confirm the increased expression of limbic system-associated membrane protein (LSAMP) in animals having the reduced exploratory activity in the elevated plus-maze. ‘Anxious’ group of rats had 1.6-fold higher expression of LSAMP gene compared to ‘non-anxious’ animals. By contrast, ‘home-cage’ control rats and ‘intermediate’ group did not differ significantly by their LSAMP gene expression level. In conclusion, it is likely that LSAMP plays a role in the regulation of exploratory behaviour of rats in the novel aversive environment

Screen for genes in periaqueductal grey of male Wistar rats related to reduced exploratory activity in the elevated plus-maze

Aim of a present study was to find genes in the periaqueductal grey (PAG) related to the exploratory behavior in rats. Male Wistar rats were divided according to their exploratory behavior in the elevated plus-maze model of anxiety into two groups: high (non-anxious) and low (anxious) exploratory activity. Differential expression of genes was analyzed using the cDNA representational difference analysis (RDA). Q-RT-PCR was used to confirm most prominent changes and functional annotation of the identified genes was performed to establish pathways related to exploratory behavior of rats. We found different genetic activation related to the exploratory activity of rats. Rats with low exploratory activity showed increase in the intracellular signal transduction and in GABA, vasopressin and adrenergic receptor activities. Functional annotation confirmed significant induction of cAMP system and GTPases in rats with anxious-type behavior. On the other hand, rats with high exploratory activity in the elevated plus-maze (non-anxious type of behavior) had increased activity of genes forming “behavioral fear response” system. These changes were specific to PAG, because they were not found in the cerebellum. In addition, plasma corticosterone levels were significantly higher in rats with non-anxious behavior compared to anxious behavior. Our results show that non-anxious behavior is related to activation of “fear response system” and more intense activation of HPA axis. Possibly it means that this system helps animals to cope with the threatening circumstances. More detailed analysis of this potential “fear response system” is necessary in the further studies for understanding its role in the regulation of emotional behavior

A screen for genes induced in the amygdaloid area during cat odor exposure

The aim of a present study was to identify the genes activated or inactivated in the amygdaloid area after the exposure to cat odor. Cat odor exposure was used to induce the ethologically relevant anxiety reaction in male rats. Differential expression of genes was analyzed using the cDNA Representational Difference Analysis (cDNA RDA). Differentially expressed mRNAs were identified by sequencing combined with database search and subsequently verified by dot blot analysis. Exposure of rats to cat odor induced avoidance of odor stimulus and suppressed the exploratory activity of animals. We found that during the cat odor exposure several genes with various functions were activated in the amygdaloid area of rat. Moreover, reverse subtraction resulted in a different set of genes that are inactivated during anxiety response. These genes can be classified according to their function as the neurotransmission related, enzymes, cell cycle regulating proteins and transcription factors. We found that during anxiety response the genes participating directly or indirectly in the synthesis of neurotransmitters (carboxypeptidase E, tyrosine 3‐monooxygenase/tryptophan 5‐mono‐oxygenase activation protein, wolframin) were up regulated. Moreover, a number of genes involved in the signal transduction (Rho GTPase, neurochondrin, Ca/calmodulin‐dependent protein kinase) were also activated. Additionally, reverse subtraction in control animals identified several up regulated genes having the antagonistic action to these genes (nischarin, Rab geranylgeranyl transferase). In conclusion, we were able to define the possible pathways linked to the regulation of anxiety response

Targeted mutation of CCK2 receptor gene modifies the behavioural effects of diazepam in female mice

Rationale Evidence suggests that GABA and CCK have opposite roles in the regulation of anxiety. Objective The aim of the present work was to study diazepam-induced anxiolytic-like action and impairment of motor co-ordination, and the parameters of benzodiazepine receptors in mice lacking CCK2 receptors. Methods The action of diazepam (0.5–3 mg/kg IP) was studied in the elevated plus-maze model of anxiety and rotarod test using mice lacking CCK2 receptors. The parameters of benzodiazepine receptors were analysed using [3H]-flunitrazepam binding. Results In the plus-maze test, the exploratory activity of the homozygous (−/−) mice was significantly higher compared to their wild-type (+/+) littermates. However, the wild-type (+/+) mice displayed higher sensitivity to the anxiolytic-like action of diazepam. Even the lowest dose of diazepam (0.5 mg/kg) induced a significant increase of open arm entries in the wild-type (+/+) mice. A similar effect in the homozygous (−/−) mice was established after the administration of diazepam 1 mg/kg. The highest dose of diazepam (3 mg/kg) caused a prominent anxiolytic-like effect in the wild-type (+/+) mice, whereas in the homozygous (−/−) animals suppression of locomotor activity was evident. The performance of the homozygous (−/−) mice in the rotarod test did not differ from that of the wild-type (+/+) littermates. However, a difference between the wild-type (+/+) and homozygous (−/−) animals became evident after treatment with diazepam. Diazepam (0.5 and 3 mg/kg) induced significantly stronger impairment of motor co-ordination in the homozygous (−/−) mice compared to their wild-type (+/+) littermates. The density of benzodiazepine binding sites was increased in the cerebellum, but not in the cerebral cortex and hippocampus, of the homozygous (−/−) mice. Conclusions Female mice lacking CCK2 receptors are less anxious than their wild-type (+/+) littermates. The reduced anxiety in homozygous (−/−) mice probably explains why the administration of a higher dose of diazepam is necessary to induce an anxiolytic-like action in these animals. The highest dose of diazepam (3 mg/kg) induced significantly stronger suppression of locomotor activity and impairment of motor co-ordination in the homozygous (−/−) mice compared to the wild-type (+/+) littermates. The increase in the action of diazepam is probably related to the elevated density of benzodiazepine receptors in the cerebellum of homozygous (−/−) mice. The present study seems to be in favour of increased tone of the GABAergic system in mice without CCK2 receptors