Molecular Factors Mediating Neural Cell Plasticity Changes in Dementia Brain Diseases

Abstract

Neural plasticity—the ability to alter a neuronal response to environmental stimuli—is an important factor in learning and memory. Short-term synaptic plasticity and long-term synaptic plasticity, including long-term potentiation and long-term depression, are the most-characterized models of learning and memory at the molecular and cellular level. These processes are often disrupted by neurodegeneration-induced dementias. Alzheimer’s disease (AD) accounts for 50% of cases of dementia. Vascular dementia (VaD), Parkinson’s disease dementia (PDD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD) constitute much of the remaining cases. While vascular lesions are the principal cause of VaD, neurodegenerative processes have been established as etiological agents of many dementia diseases. Chief among such processes is the deposition of pathological protein aggregates in vivo including β-amyloid deposition in AD, the formation of neurofibrillary tangles in AD and FTD, and the accumulation of Lewy bodies composed of α-synuclein aggregates in DLB and PDD. The main symptoms of dementia are cognitive decline and memory and learning impairment. Nonetheless, accurate diagnoses of neurodegenerative diseases can be difficult due to overlapping clinical symptoms and the diverse locations of cortical lesions. Still, new neuroimaging and molecular biomarkers have improved clinicians’ diagnostic capabilities in the context of dementia and may lead to the development of more effective treatments. Both genetic and environmental factors may lead to the aggregation of pathological proteins and altered levels of cytokines, such that can trigger the formation of proinflammatory immunological phenotypes. This cascade of pathological changes provides fertile ground for the development of neural plasticity disorders and dementias. Available pharmacotherapy and disease-modifying therapies currently in clinical trials may modulate synaptic plasticity to mitigate the effects neuropathological changes have on cognitive function, memory, and learning. In this article, we review the neural plasticity changes seen in common neurodegenerative diseases from pathophysiological and clinical points of view and highlight potential molecular targets of disease-modifying therapies.

Alteration in the number of neuronal and non-neuronal cells in mouse models of obesity

“… 61 Molecular modifications in the hippocampus, such as microglial activation, decreased neurogenesis and apoptosis, are directly related to the onset of dementia. 61 , 62 Moreover, studies using diet-induced obesity models demonstrated that neuroinflammation is an important feature of obesity, including in the hippocampus, 63 that is associated with decreased neurogenesis, 15 , 64 cognitive impairment 56 , 65 and activation of apoptosis. 66 In obesity, adipocytes produce pro-inflammatory cytokines that can cross the blood–brain barrier (BBB) and induce microglial activation and neuronal damage.…”

Ameliorative Processes of Beta-Carotene in Streptozotocin-Induced Diabetic Vascular Dementia in Rats

“…The hippocampus is the most sensitive region of the brain and most susceptible to ischemia and hypoxia, particularly the CA1 region [45]. Various brain areas work in coordination for different types of cognitive functions [46]. Other than the hippocampal area, the entorhinal cortex, prefrontal cortex, cerebellum, septum, amygdala, and pons play a crucial role in memory function.…”

Selected Biomarkers of Oxidative Stress and Energy Metabolism Disorders in Neurological Diseases

“…These organelles convert energy to adenosine triphosphate (ATP), which neurons need to regulate, among other neurotransmissions [ 1 ]. Moreover, ATP plays a crucial role in processes related to maintaining neuronal plasticity [ 7 , 8 ]. Mitochondria are not only the main energy producers in cells but also the main source of reactive oxygen species (ROS).…”