scholarly journals General Anesthesia During Neurodevelopment Reduces Autistic Behavior in Adult BTBR Mice, a Murine Model of Autism

2021 ◽  
Vol 15 ◽  
Author(s):  
Jianchen Cui ◽  
Jiho Park ◽  
Xianshu Ju ◽  
Yulim Lee ◽  
Boohwi Hong ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Critical Period ◽  
Repetitive Behavior ◽  
Sevoflurane Anesthesia ◽  
Autistic Behavior ◽  
Inhibitory Synaptic Transmission ◽  
Synaptic Changes ◽  
Bdnf Signaling ◽  
And Behavior

Preclinical studies suggest that repeated exposure to anesthetics during a critical period of neurodevelopment induces long-term changes in synaptic transmission, plasticity, and behavior. Such changes are of great concern, as similar changes have also been identified in animal models of neurodevelopmental disorders (NDDs) such as autism. Because of overlapping synaptic changes, it is also possible that anesthetic exposures have a more significant effect in individuals diagnosed with NDDs. Thus, we evaluated the effects of early, multiple anesthetic exposures in BTBR mice, an inbred strain that displays autistic behavior. We discovered that three cycles of sevoflurane anesthesia (2.5%, 1 h) with 2-h intervals between each exposure in late postnatal BTBR mice did not aggravate, but instead improved pathophysiological mechanisms involved with autistic behavior. Sevoflurane exposures restored E/I balance (by increasing inhibitory synaptic transmission), and increased mitochondrial respiration and BDNF signaling in BTBR mice. Most importantly, such changes were associated with reduced autistic behavior in BTBR mice, as sociability was increased in the three-chamber test and repetitive behavior was reduced in the self-grooming test. Our results suggest that anesthetic exposures during neurodevelopment may affect individuals diagnosed with NDDs differently.

scholarly journals The Kinase Function of MSK1 Regulates BDNF Signaling to CREB and Basal Synaptic Transmission, But Is Not Required for Hippocampal Long-Term Potentiation or Spatial Memory

eNeuro ◽  
2017 ◽  
Vol 4 (1) ◽  
pp. ENEURO.0212-16.2017 ◽  
Author(s):  
Stephanie Daumas ◽  
Christopher J. Hunter ◽  
Rajen B. Mistry ◽  
Lorenzo Morè ◽  
Lucia Privitera ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Spatial Memory ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Bdnf Signaling ◽  
Basal Synaptic Transmission

Adolescent Substance Abuse, Transgenerational Consequences and Epigenetics

2021 ◽  
Vol 19 ◽  
Author(s):  
Hamed Salmanzadeh ◽  
Mohammad Ahmadi-Soleimani ◽  
Maryam Azadi ◽  
Robert F. Halliwell ◽  
Hossein Azizi
Keyword(s):  
Substance Abuse ◽  
Clinical Studies ◽  
Critical Period ◽  
Drug Exposure ◽  
Drugs Of Abuse ◽  
Transitional Period ◽  
Drug Actions ◽  
And Behavior ◽  
Human Brains

: Adolescence is the transitional period between childhood and adulthood and a critical period in brain development. Adolescence in humans is also associated with increased expression of risk-taking behaviors. Epidemiological and clinical studies, for example, show a surge of drug abuse and raise the hypothesis that the adolescent brain undergoes critical changes resulting in diminished control. Determining how substance abuse during this critical period might cause long-term neurobiological changes in cognition and behavior is therefore critically important. The present work aims to provide an evaluation of the transgenerational and multi- generational phenotypes derived from parent animals exposed to drugs of abuse only during their adolescence. Specifically, we will consider changes found following administration of cannabinoids, nicotine, alcohol and opiates. In addition, epigenetic modifications of the genome following drug exposure will be discussed as emerging evidence of the underlying adverse transgenerational effects. Notwithstanding, much of the new data discussed here is from animal models, indicating that future clinical studies are much needed to better understand the neurobiological consequences and mechanisms of drug actions on the human brains’ development and maturation.

scholarly journals Impact of Chronic BDNF Depletion on GABAergic Synaptic Transmission in the Lateral Amygdala

2019 ◽  
Vol 20 (17) ◽  
pp. 4310 ◽  
Author(s):  
Susanne Meis ◽  
Thomas Endres ◽  
Thomas Munsch ◽  
Volkmar Lessmann
Keyword(s):  
Synaptic Transmission ◽  
Long Term Potentiation ◽  
Fear Learning ◽  
Inhibitory Synapses ◽  
Lateral Amygdala ◽  
Term Potentiation ◽  
Gabaergic Synapses ◽  
Bdnf Signaling ◽  
The Impact

Brain-derived neurotrophic factor (BDNF) has previously been shown to play an important role in glutamatergic synaptic plasticity in the amygdala, correlating with cued fear learning. While glutamatergic neurotransmission is facilitated by BDNF signaling in the amygdala, its mechanism of action at inhibitory synapses in this nucleus is far less understood. We therefore analyzed the impact of chronic BDNF depletion on GABAA-mediated synaptic transmission in BDNF heterozygous knockout mice (BDNF+/−). Analysis of miniature and evoked inhibitory postsynaptic currents (IPSCs) in the lateral amygdala (LA) revealed neither pre- nor postsynaptic differences in BDNF+/− mice compared to wild-type littermates. In addition, long-term potentiation (LTP) of IPSCs was similar in both genotypes. In contrast, facilitation of spontaneous IPSCs (sIPSCs) by norepinephrine (NE) was significantly reduced in BDNF+/− mice. These results argue against a generally impaired efficacy and plasticity at GABAergic synapses due to a chronic BDNF deficit. Importantly, the increase in GABAergic tone mediated by NE is reduced in BDNF+/− mice. As release of NE is elevated during aversive behavioral states in the amygdala, effects of a chronic BDNF deficit on GABAergic inhibition may become evident in response to states of high arousal, leading to amygdala hyper-excitability and impaired amygdala function.

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