Modulation of vascular endothelial growth factor (VEGF) expression in motor neurons and its electrophysiological effects

Abstract

Previous studies have shown that VEGF expression in forebrain increases after experimental manipulations that increase neuronal activity [6,12]. One question is whether this also occurs in motor neurons. If so, it could be potentially advantageous from a therapeutic perspective, because VEGF prevents motor neuron degeneration [2,10,24]. Therefore, we asked whether endogenous VEGF expression in motor neurons could be modulated. We also asked what VEGF exposure would do to motor neurons using electrophysiology.Immunocytochemistry showed that motor neuron VEGF expression increased after a stimulus that increases neuronal and motor activity, i.e., convulsions. The increase in VEGF immunoreactivity occured in all motor neuron populations that were examined 24 hrs later. This effect was unlikely to be due to seizure-induced toxicity, because silver degeneration stain did not show the typical appearance of a dying or dead neuron.

Vascular Endothelial Growth Factor Attenuates Neurodegenerative Changes in the NSC-34 Motor Neuron Cell Line Induced by Cerebrospinal Fluid of Sporadic Amyotrophic Lateral Sclerosis Patients

“…Our observations compare well with those of McCloskey et al [21] , who in a recent study demonstrated that exogenous exposure to VEGF at a concentration of 200 ng/ml under normal conditions depressed the stimulus-evoked depolarization of hypoglossal motor neurons. They considered this depression as a compensatory mechanism, failure of which would result in excessive firing of motor neurons and probable motor neuron loss comparable to that seen in ALS [21] . Thus, it is likely that addition of exogenous VEGF in normal cultures lowered the normal cellular, biochemical and physiological processes of the differentiated cells resulting in reduced ChAT expression.…”

Angiogenesis in multiple sclerosis and experimental autoimmune encephalomyelitis

“…Another study reported a decreased VEGF level not only in neurons but also in astroglia in a rat EAE experimental model [53]. A VEGF decrease may be caused by neuronal dysfunction, as already demonstrated in epilepsy by McCloskey et al [54]. Astroglial production of VEGF is enhanced in pathological conditions, including human astrocytoma [55] and MS and EAE, to promote angiogenesis and glial survival [50].…”

VEGF production and signaling in Müller glia are critical to modulating vascular function and neuronal integrity in diabetic retinopathy and hypoxic retinal vascular diseases

“…Anti-VEGF clinical trials demonstrate huge variations in responses to long-term treatment, a portion of patients had a reduction in visual acuity. While this could be due to multiple factors, the so-called physiological levels of VEGF are most likely different from one patient to another, which are essential to protecting retinal cells and neurons and regulating neuronal function (35–41). In short, a suitable physiological level for one patient could potentially be harmful to retinal integrity in others.…”

“…Gene targeting analysis suggests that VEGF and semaphorins-mediated neuropilin-2 signaling is important to the migration of gonadotropin-releasing hormone neurons in the neuroendocrine system (53). VEGF has been suggested to reduce excessive excitation of hypoglossal motor neurons by downregulating stimulus-evoked depolarization, a critical mechanism to prevent ALS (35). VEGF is capable of downregulating synaptic responses significantly in hippocampal principal neurons in rats, which may be critical to the onset of epilepsy (36).…”