Are you synapse rich & Energy Poor?

Synapses: The Brain’s Energy-Demanding Sites (2022)

The brain is one of the most energy-consuming organs in the mammalian body, and synaptic transmission is one of the major contributors. To meet these energetic requirements, the brain primarily uses glucose, which can be metabolized through glycolysis and/or mitochondrial oxidative phosphorylation.

Deep proteomics identifies shared molecular pathway alterations in synapses of patients with schizophrenia and bipolar disorder and mouse model (2023)

Abstract

Synaptic dysfunction is implicated in the pathophysiology of schizophrenia (SCZ) and bipolar disorder (BP).

We use quantitative mass spectrometry to carry out deep, unbiased proteomic profiling of synapses purified from the dorsolateral prefrontal cortex of 35 cases of SCZ, 35 cases of BP, and 35 controls.

Compared with controls, SCZ and BP synapses show substantial and similar proteomic alterations.

Network analyses reveal upregulation of proteins associated with autophagy and certain vesicle transport pathways and downregulation of proteins related to synaptic, mitochondrial, and ribosomal function in the synapses of individuals with SCZ or BP.

Some of the same pathways are similarly dysregulated in the synaptic proteome of mutant mice deficient in Akap11, a recently discovered shared risk gene for SCZ and BP.

Our work provides biological insights into molecular dysfunction at the synapse in SCZ and BP and serves as a resource for understanding the pathophysiology of these disorders.

TREMendous 2 Be Social (2018)

Abstract

TREM2 is known for its role in microglial phagocytosis and in neurodegenerative diseases.

In this issue of Immunity, Filipello et al. (2018) show that microglial TREM2 is required for synaptic pruning in early development.

TREM2-deficient mice show altered social behavior in adulthood, linking TREM2 to neurodevelopmental disease.

Microglia at the Tripartite Synapse during Postnatal Development: Implications for Autism Spectrum Disorders and Schizophrenia (2023)

Abstract

Synapses are the fundamental structures of neural circuits that control brain functions and behavioral and cognitive processes.

Synapses undergo formation, maturation, and elimination mainly during postnatal development via a complex interplay with neighboring astrocytes and microglia that, by shaping neural connectivity, may have a crucial role in the strengthening and weakening of synaptic functions, that is, the functional plasticity of synapses.

Indeed, an increasing number of studies have unveiled the roles of microglia and astrocytes in synapse formation, maturation, and elimination as well as in regulating synaptic function.

Over the past 15 years, the mechanisms underlying the microglia- and astrocytes-dependent regulation of synaptic plasticity have been thoroughly studied, and researchers have reported that the disruption of these glial cells in early postnatal development may underlie the cause of synaptic dysfunction that leads to neurodevelopmental disorders such as autism spectrum disorder (ASD) and schizophrenia.

The Synaptic and Circuit Functions of Vitamin D in Neurodevelopment Disorders (2023)

 Abstract

Vitamin D deficiency/insufficiency is a public health issue around the world.

According to epidemiological studies, low vitamin D levels have been associated with an increased risk of some neurodevelopmental disorders, including autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD).

Animal models reveal that vitamin D has a variety of impacts on the synapses and circuits in the brain. A lack of vitamin D affects the expression of synaptic proteins, as well as the synthesis and metabolism of various neurotransmitters.

Depending on where vitamin D receptors (VDRs) are expressed, vitamin D may also regulate certain neuronal circuits through the endocannabinoid signaling, mTOR pathway and oxytocin signaling.

While inconsistently, some data suggest that vitamin D supplementation may be able to reduce the core symptoms of ASD and ADHD.

This review emphasizes vitamin D's role in the synaptic and circuit mechanisms of neurodevelopmental disorders including ASD and ADHD.

Future application of vitamin D in these disorders will depend on both basic research and clinical studies, in order to make the transition from the bench to the bedside.

Lack of neuron ‘pruning’ may be behind many brain-related conditions (2023)

Brain scans show that adolescents with more symptoms of certain mental health conditions, autism or ADHD have undergone less pruning than usual of synaptic connections between neurons."