DL-3-n-butylphthalide enhances synaptic plasticity in mouse model of brain impairments

Synaptic impairment results in cognitive dysfunction of Alzheimer’s disease (AD). As a plant extract, it is found that DL-3-n-butylphthalide (L-NBP) rescues abnormal cognitive behaviors in AD animals. However, the regulatory effects of L-NBP on synaptic plasticity remains unclear. APP/PS1 mice at 12 months old received oral L-NBP treatment for 12 weeks. A water maze test assessed cognitive performances. In vitro patch-clamp recordings and in vivo field potential recordings were performed to evaluate synaptic plasticity. The protein expression of AMPA receptor subunits (GluR1 and GluR2) and NMDA receptor subunits (NR1, NR2A, and NR2B) was examined by Western blot. In addition, glutaminase activity and glutamate level in the hippocampus were measured by colorimetry to evaluate presynaptic glutamate release. L-NBP treatment could significantly improve learning and memory ability, upregulate NR2A and NR2B protein expressions, increase glutaminase activity and glutamate level in the hippocampus, and attenuate synaptic impairment transmission in the AD mice. L-NPB plays a beneficial role in AD mice by regulating NMDA receptor subunits’ expression and regulating presynaptic glutamate release.

Caudate nucleus volume mediates the link between glutamatergic neurotransmission and problematic smartphone use in youth

Background and aimsProblematic smartphone use (PSU) is growing rapidly among teens. It has similar presentations as other behavioral addictions in terms of excessive use, impulse control problems, and negative consequences. However, the underlying neurobiological mechanisms remain undiscovered. We hypothesized that structural changes in the striatum might serve as an important link between alteration in glutamate signaling and development of PSU.MethodsAmong 88 participants, twenty (F:M, 12:8; age 16.2 ± 1.1) reported high scores in the smartphone addiction proneness scale (SAPS) with a cut-off score of 42; the other 68 (F:M, 19:49; age 15.3 ± 1.7) comprised the control group. Sociodemographic data and depression, anxiety, and impulsivity traits were measured. Striatal volumes (caudate, putamen, and nucleus accumbens) were estimated from T1 imaging data. Serum glutamate levels were estimated from peripheral blood samples. Group comparisons of each data were performed after controlling for age and gender. Mediation analyses were conducted to test the indirect effects of glutamate level alteration on PSU through striatal volumetric alteration.ResultsThe PSU group showed a decrease in both caudate volumes than the control group. Left caudate volume was positively correlated with serum glutamate level, and negatively with impulsivity traits and SAPS scores. The mediation model revealed a significant indirect effect of serum glutamate on SAS scores through the reduced left caudate volume.Discussion and conclusionsThis study suggests that altered glutamatergic neurotransmission may be associated with PSU among teens, possibly through reduced left caudate volume. Current findings might support neural mechanisms of smartphone addiction.

Vestibular stimulation induced alteration in glutamate levels improves memory and anxiety scores in scopolamine induced dementia rats

Glutamate is an excitatory neurotransmitter which is essential for cognition but, at the same time, a neurotoxin if accumulated beyond a certain level. The derangement of glutamate level in brain is closely associated with Alzheimer’s disease. Vestibular stimulation is known to stabilize various neuro-chemical transmission in central nervous system, especially effective in enhancing acetyl choline level and reduction of acetyl cholinesterase level. So the current study has undertaken to evaluate glutamate level in dementia and vestibular stimulation groups and its role in improving memory and anxiety scores. In the present study, 32 Wistar rats were used. Scopolamine was used to induce dementia and caloric stimulation (bilateral, unilateral right and unilateral left) was used stimulate vestibular system. Behavioral parameters like water maze used to asses memory and elevated plus maze was used to assess anxiety in our study. Glutamate was quantified by spectroflurimetry and histopathology of hippocampus and cortex were assessed. Caloric vestibular stimulation effectively reduced glutamate level near to normal values and this result reflected in increased memory scores in water maze and increased exploratory activities in elevated plus maze. Especially unilateral left vestibular stimulation has found beneficial in reducing glutamate level. All these positive outcomes have proven that vestibular stimulation can increase memory and anxiety scores in dementia and thereby can be used as an alternative therapy in this field. Further animal studies and human studies are needed to dig deep into the molecular mechanisms behind its actions.

OR33-05 Amino Acid Signature of Abdominal Obesity in the TwinsUK Cohort

Background and aim: Metabolomic studies have shown that circulating amino acid levels are altered in the context of obesity. The branched-chain amino acids (BCAAs, namely leucine, isoleucine and valine) have been the most studied because of their consistent positive association with adiposity and their ability to prospectively predict type 2 diabetes and cardiovascular diseases (1). Circulating glutamate has been much less investigated, but some have shown that its specific association with central fat accumulation was stronger than that of BCAAs (2). This study aimed to evaluate the relationship between circulating glutamate and abdominal obesity and the impact of genetic factors on this association. Methods: In the TwinsUK cohort, we selected individuals for whom both metabolomics and DXA trunk fat measurements were available (n=4 665). We used linear regression to assess the correlation between glutamate level and trunk fat. Those with a trunk fat mass greater than 15 kg were considered abdominally obese. We compared the odds of presenting abdominal obesity in each circulating glutamate quintile with logistic regression models. Monozygotic twin pairs discordant for trunk fat were selected to identify analyte differences driven by non-genetic factors. All analyses were also performed with BCAAs for comparison. Results: Circulating glutamate was positively and significantly associated with trunk fat (β: 0.28, 95%CI: 0.26-0.31). Individuals in the highest circulating glutamate quintile had a more than 8-fold higher risk of being characterized by abdominal obesity compared to those in the lowest quintile (OR: 8.44, 95%CI: 6.17-11.55). In the 54 monozygotic twin pairs discordant for trunk fat, the heavier twin had significantly higher glutamate level compared to the leaner co-twin (p-value: 4.05e-07). In all these analyses, the results for glutamate were more significant than with any of the BCAAs. Conclusion: There is a positive relationship between circulating glutamate and trunk fat that is partially independent of genetic background. This often-overlooked metabolite might represent an interesting biomarker of abdominal obesity. References: (1) Newgard (2017). Metabolomics and Metabolic Diseases: Where Do We Stand? Cell Metab, 25(1), 43-56, (2) Kimberly et al. (2017). Metabolite profiling identifies anandamide as a biomarker of nonalcoholic steatohepatitis. JCI Insight, 2(9).