Symmetric and Asymmetric Synapses Driving Neurodegenerative Disorders

Abstract

In 1959, E. G. Gray described two different types of synapses in the brain for the first time: symmetric and asymmetric. Later on, symmetric synapses were associated with inhibitory terminals, and asymmetric synapses to excitatory signaling. The balance between these two systems is critical to maintain a correct brain function. Likewise, the modulation of both types of synapses is also important to maintain a healthy equilibrium. Cerebral circuitry responds differently depending on the type of damage and the timeline of the injury. For example, promoting symmetric signaling following ischemic damage is beneficial only during the acute phase; afterwards, it further increases the initial damage. Synapses can be also altered by players not directly related to them; the chronic and long-term neurodegeneration mediated by tau proteins primarily targets asymmetric synapses by decreasing neuronal plasticity and functionality. Dopamine represents the main modulating system within the central nervous system. Indeed, the death of midbrain dopaminergic neurons impairs locomotion, underlying the devastating Parkinson’s disease. Herein, we will review studies on symmetric and asymmetric synapses plasticity after three different stressors: symmetric signaling under acute damage—ischemic stroke; asymmetric signaling under chronic and long-term neurodegeneration—Alzheimer’s disease; symmetric and asymmetric synapses without modulation—Parkinson’s disease.

Alzheimer’s Disease Seen through the Eye: Ocular Alterations and Neurodegeneration

“…In summary, there is no consensus regarding the presence of Aβ and tau deposits in retinas from either animal models or AD patients. Based on the literature, it is plausible that Aβ or tau or both could be found in AD retinas due to seeding [ 105 ]. However, the lack of consistent evidence in both animal and clinical research requires further studies to decipher the role of such accumulations in retinal neuronal fate and how this affects the retinal AD phenotype.…”

Involvement of Ceramide Metabolism in Cerebral Ischemia

“…Mechanical thrombectomy and thrombolysis are the reperfusion strategies, which are based on the restoration of the CBF. Neurorepair involves the restoration of brain function by regenerating the damaged cerebral tissue or establishing alternative neural pathways or synapses ( Kim J. H. et al, 2021 ; Romaus-Sanjurjo et al, 2021 ). Neuroprotection has been focused on reducing cell death after an ischemic event intervening in the ischemic cascade mechanisms such as inflammation, oxidative stress, endothelial damage, or excitotoxicity ( Chamorro et al, 2016 ).…”