Targeting acetyl-CoA metabolism attenuates the formation of fear memories through reduced activity-dependent histone acetylation.

Histone acetylation is a key component in the consolidation of long-term fear memories. Histone acetylation is fueled by acetyl-coenzyme A (acetyl-CoA), and recently, nuclear-localized metabolic enzymes that produce this metabolite have emerged as direct and local regulators of chromatin. In particular, acetyl-CoA synthetase 2 (ACSS2) mediates histone acetylation in the mouse hippocampus. However, whether ACSS2 regulates long-term fear memory remains to be determined. Here, we show that Acss2 knockout is well tolerated in mice, yet the Acss2-null mouse exhibits reduced acquisition of long-term fear memory. Loss of Acss2 leads to reductions in both histone acetylation and expression of critical learning and memory-related genes in the dorsal hippocampus, specifically following fear conditioning. Furthermore, systemic administration of blood-brain barrier-permeable Acss2 inhibitors during the consolidation window reduces fear-memory formation in mice and rats and reduces anxiety in a predator-scent stress paradigm. Our findings suggest that nuclear acetyl-CoA metabolism via ACSS2 plays a critical, previously unappreciated, role in the formation of fear memories.

Heat-Stress Preconditioning Attenuates Behavioral Responses to Psychological Stress: The Role of HSP-70 in Modulating Stress Responses.

Exposure to high ambient temperature is a stressor that influences both biological and behavioral functions and has been previously shown to have an extensive impact on brain structure and function. Physiological, cellular and behavioral responses to heat-stress (HS) (40-41 °C, 2 h) were evaluated in adult male Sprague-Dawley rats. The effect of HS exposure before predator-scent stress (PSS) exposure (i.e., HS preconditioning) was examined. Finally, a possible mechanism of HS-preconditioning to PSS was investigated. Immunohistochemical analyses of chosen cellular markers were performed in the hippocampus and in the hypothalamic paraventricular nucleus (PVN). Plasma corticosterone levels were evaluated, and the behavioral assessment included the elevated plus-maze (EPM) and the acoustic startle response (ASR) paradigms. Endogenous levels of heat shock protein (HSP)-70 were manipulated using an amino acid (L-glutamine) and a pharmacological agent (Doxazosin). A single exposure to an acute HS resulted in decreased body mass (BM), increased body temperature and increased corticosterone levels. Additionally, extensive cellular, but not behavioral changes were noted. HS-preconditioning provided behavioral resiliency to anxiety-like behavior associated with PSS, possibly through the induction of HSP-70. Targeting of HSP-70 is an attractive strategy for stress-related psychopathology treatment.

Influence of muscle depth and thickness on ultrasound echo intensity of the vastus lateralis.

BACKGROUND: Ultrasonography is used to evaluate muscle quality (i.e. echo intensity [EI]), but an attenuation of ultrasound waves occurs in deeper tissues, potentially affecting these measures. PURPOSE: To determine whether muscle thickness (MT) affects EI and if EI varies between the superficial and deep portions of the muscle. MATERIALS AND METHODS: MT, EI, subcutaneous adipose tissue thickness (SAT), tissue depth (DISDEEP), and EI of the overall (EIFULL) as well as deep (EIDEEP) and superficial (EISUPF) portions of the vastus lateralis (VL) were assessed in 33 resistance-trained males using ultrasonography. The difference (EIDIFF) between EISUPF and EIDEEP was calculated. Mean differences between EIFULL, EISUPF, and EIDEEP were analyzed using a repeated-measures analysis of variance (ANOVA). Relationships between measures of muscle depth/ thickness and EI were examined using Pearson's r. RESULTS: EISUPF was greater than EIDEEP (P < 0.001) and EIFULL (P < 0.001). MT was negatively correlated with EIFULL (P < 0.001) and positively correlated with EIDIFF (P < 0.001). SAT was not correlated with any EI measure, but DISDEEP was positively correlated with EIDIFF (P < 0.001). CONCLUSION: EI of the VL is heterogeneous, as the deeper portion produces lower values than the superficial portion. Thicker muscles present lower EI but have greater discrepancies in EI between the superficial and deep portions. Although SAT was not correlated with EI, DISDEEP was related to EIDIFF, demonstrating that the combination of MT and SAT should be considered when evaluating muscle quality. Future research is necessary to determine if changes in EI following resistance training are driven by increases in MT.

ß-Alanine Supplementation Attenuates the Neurophysiological Response in Animals Exposed to an Acute Heat Stress.

The effect of 30 days of ß-alanine supplementation on neurophysiological responses of animals exposed to an acute heat stress (HS) was examined. Animals were randomized to one of three groups; exposed to HS (120 min at 40-41 °C) and fed a normal diet (EXP; n = 12); EXP and supplemented with ß-alanine (EXP + BA; n = 10); or not exposed (CTL; n = 10). Hippocampal (CA1, CA3 and DG) and hypothalamic (PVN) immunoreactive (ir) cell numbers of COX2, IBA-1, BDNF, NPY and HSP70 were analyzed. Three animals in EXP and one in EXP-BA did not survive the HS, however no significant difference (p = 0.146) was noted in survival rate in EXP + BA. The % change in rectal temperature was significantly lower (p = 0.04) in EXP + BA than EXP. Elevations (p's < 0.05) in COX-2, IBA-1 and HSP70 ir-cell numbers were noted in animals exposed to HS in all subregions. COX-2 ir-cell numbers were attenuated for EXP + BA in CA1 (p = 0.02) and PVN (p = 0.015) compared to EXP. No difference in COX-2 ir-cell numbers was noted between CTL and EXP + BA at CA1. BDNF-ir cell numbers in CA1, DG and PVN were reduced (p's < 0.05) during HS compared to CTL. No difference in BDNF-ir cell numbers was noted between EXP + BA and CTL in CA3 and PVN. NPY-ir density was reduced in exposed animals in all subregions, but NPY-ir density for EXP-BA was greater than EXP in CA3 (p < 0.001) and PVN (p = 0.04). ß-Alanine supplementation attenuated the thermoregulatory and inflammatory responses and maintained neurotrophin and neuropeptide levels during acute HS. Further research is necessary to determine whether ß-alanine supplementation can increase survival rate during a heat stress.

Effects of Rest Position on Morphology of the Vastus Lateralis and Its Relationship with Lower-Body Strength and Power.

Ultrasonography of the lower body typically encompasses supine rest due to fluid shifts affecting tissue size and composition. However, vastus lateralis (VL) examination is completed in the lateral recumbent position, and this positional change may influence morphology and its ability to predict function. This study aimed to examine the effect of position on VL morphology and its relationship with lower-body performance. Cross-sectional area (CSA), muscle thickness (MT), pennation angle (PA), echo intensity (UnCorEI), subcutaneous adipose tissue thickness (SFT), and echo intensity corrected for SFT (CorEI) were assessed in 31 resistance-trained males (23.0 ± 2.1 yrs; 1.79 ± 0.08 m; 87.4 ± 11.7 kg) immediately after transitioning from standing to supine (IP), after 15 min of standing (ST), and after 15 min of rest in three recumbent positions: supine (SUP), dominant lateral recumbent (DLR), non-dominant lateral recumbent (NDLR). Participants also completed unilateral vertical jumps, isometric/isokinetic tests, and a one-repetition maximum leg press. CSA, MT, PA, and SFT were greater in ST compared to NDLR, DLR, and SUP (p < 0.05). CSA, UnCorEI, and CorEI were different between recumbent positions; however no differences were observed for MT, PA, and SFT. Different magnitudes of relationships were observed between muscle morphological characteristics measured after rest in different positions and performance variables. Muscle morphology in IP generally appears to be the best predictor of performance for most variables, although utilizing the NDLR and DLR positions may provide comparable results, whereas morphology measured in ST and SUP provide weaker relationships with physical performance. IP also requires less time and fewer requirements on the technician and subject, thus researchers should consider this positioning for VL examination.