Inhibiting silence information regulator 2 and glutaminase in the amygdala can improve social behavior in autistic rats / 浙江大学学报·医学版

OBJECTIVE@#To investigate the underlying molecular mechanisms by which silence information regulator (SIRT) 2 and glutaminase (GLS) in the amygdala regulate social behaviors in autistic rats.@*METHODS@#Rat models of autism were established by maternal sodium valproic acid (VPA) exposure in wild-type rats and SIRT2-knockout ( SIRT2 -/-) rats. Glutamate (Glu) content, brain weight, and expression levels of SIRT2, GLS proteins and apoptosis-associated proteins in rat amygdala at different developmental stages were examined, and the social behaviors of VPA rats were assessed by a three-chamber test. Then, lentiviral overexpression or interference vectors of GLS were injected into the amygdala of VPA rats. Brain weight, Glu content and expression level of GLS protein were measured, and the social behaviors assessed.@*RESULTS@#Brain weight, amygdala Glu content and the levels of SIRT2, GLS protein and pro-apoptotic protein caspase-3 in the amygdala were increased in VPA rats, while the level of anti-apoptotic protein Bcl-2 was decreased (all P<0.01). Compared with the wild-type rats, SIRT2 -/- rats displayed decreased expression of SIRT2 and GLS proteins in the amygdala, reduced Glu content, and improved social dysfunction (all P<0.01). Overexpression of GLS increased brain weight and Glu content, and aggravated social dysfunction in VPA rats (all P<0.01). Knockdown of GLS decreased brain weight and Glu content, and improved social dysfunction in VPA rats (all P<0.01).@*CONCLUSIONS@#The glutamate circulatory system in the amygdala of VPA induced autistic rats is abnormal. This is associated with the upregulation of SIRT2 expression and its induced increase of GLS production; knocking out SIRT2 gene or inhibiting the expression of GLS is helpful in maintaining the balanced glutamate cycle and in improving the social behavior disorder of rats.

Aspirin: a neuroprotective agent at high doses?

Aspirin, acetylsalicylic acid, is routinely used in clinics as an analgesic, antipyretic and in the secondary prevention of stroke. These effects are caused by low doses of the drug (0.3-3.6 g/day) through the inhibition of cyclo-oxygenase, the enzyme responsible for prostaglandin synthesis. Higher doses of aspirin (4-6 g/day) are used in the treatment of inflammatory conditions such as rheumatoid arthritis and recent laboratory findings suggest that it could play a role in neuroprotection against glutamate excitotoxicity. This article reviews the possible mechanisms of action of high-dose aspirin in neuroprotection.

Influence of different forms of nitrogen on uptake of ammonium, glutamate and glutamine in the cyanobacterium Nostoc muscorum.

Effect of various types of nitrogen nutrition was studied on the uptake of ammonium, glutamate and glutamine by Nostoc muscorum and its Het-Nif- mutant. Ammonium nitrogen acted as a potent inhibitor/repressor of ammonium, glutamate and glutamine transport. Nitrate nitrogen was found to be a strong inhibitor/repressor of ammonium transport, a partial inhibitor/repressor of glutamate transport but, caused a partial stimulation of glutamine transport.

Products of non-reductive CO2 assimilation in the halophilic archaebacterium Haloferax mediterranei.

The products of CO2 fixation by heterotrophically grown Haloferax mediterranei were analysed. The main 14C-labelled alpha-ketoacid detected following incubation with NaH14CO3 and pyruvate or propionate was pyruvate. In presence of these organic acids and NH4+, 14CO2 was incorporated into glutamic and aspartic acids and alanine.

A study on the role of N-methyl-D-aspartate receptors in the rat visual cortex

The amino acid L-glutamate is a major excitatory neurotransmitter in the central nervous system of vertebrates(1). NMDA (N-methyl-d-aspartate) is one of the L-glutamate receptor subtypes(2). During a critical period of early postnatal development, the visual cortex is susceptible to experience-dependent modification of neuronal responses. Recently, the activation of NMDA receptors has been supposed as a prerequisite for the induction of such modification(3). We therefore investigated developmental changes of NMDA receptors in the rat visual cortex and questioned whether they could be related to the visual development. We assessed the density of [(3)H]-NMDA receptor in the visual cortex of normally reared rate (Group I) and visually deprived rats (Group II) using quantitative autoradiography(4). The density of [(3)H]-NMDA receptor was significantly lower in Group II than in group I during the early postnatal period, and increased rapidly by postnatal 1 week and, decreased after postnatal 5 weeks. These results suggested that NMDA receptors may play a role in neuronal development in the visual cortex during the early postnatal period.

Sulpiride in Meige's Syndrome: Possible Role of Glutamate

Sulpiride, a selective antagonist for adenylate cyclase-independent dopamine receptors, was administrated to 25 patients with blepharospasm and oromandibular dystonia(Meige's syndrome). Of the 25, 7 patients (28%) exhibited marked and lasting improvement with sulpiride and 12 patients (48%) showed mild or transient improvement. This favorable therapeutic response to sulpiride suggests that striatal glutamate underactivity may play a role in the pathophysiology of Meige's syndrome as a primary or secondary defect.