Clonidine Treatment Delays Postnatal Motor Development and Blocks Short-Term Memory in Young Mice

Abstract

During the development of the nervous system, the perinatal period is particularly sensitive as neuronal connections are still forming in the brain of the neonate. Alpha2-adrenergic receptors are overexpressed temporarily in proliferative zones in the developing brain, reaching a peak during the first postnatal week of life. Both stimulation and blocking of these receptors during this period alter the development of neural circuits, affecting synaptic connectivity and neuronal responses. They even affect motor and cognitive skills later on in the adult. It's especially important to look for the early neurological consequences resulting from such modifications, because they may go unnoticed. The main objective of the present study has been to reaffirm the importance of the maturation of alpha-adrenergic system in mice, by carrying out a comprehensive examination of motor, behavioral and cognitive effects in neonates, during early postnatal development, following chronic administration of the drug Clonidine, an alpha2 adrenergic system agonist. Our study shows that mice treated postnatally with clonidine present a temporal delay in the appearance of developmental markers, a slow execution of vestibular reflexes during first postnatal week of life and a blockade of the short term memory in the novel object recognition task. Shortly after the treatment the startle response is hyperreactive.

Maternal exercise during pregnancy modulates mitochondrial function and redox status in a sex-dependent way in adult offspring’s skeletal muscle

“…Moreover, studies also demonstrated that exercise increases the expression of estrogen receptors alpha (ERα) that are found in skeletal muscle, including in mitochondria, which is associated with the increase in mitochondrial function. 22,56,57 In this way, estrogen may be potentially acting in cell signaling and stimulating the expression of Mn-SOD, or simply acting as an oxidant scavenger, due to its structural similarity to other antioxidants like vitamin E, 55 which can explain the reduced oxidant content and also the antioxidant network, found in the females in our model. Unfortunately, we did not evaluate the estrous cycle on females and the hormonal profile of the groups to answer this specific hypothesis in our study.…”

ADCK2 Haploinsufficiency Reduces Mitochondrial Lipid Oxidation and Causes Myopathy Associated with CoQ Deficiency

“…Muscle force in mice was measured in vivo using a Grip Strength Columbus apparatus (Cibertec SA) as indicated [39]. Behavior was analyzed by passive avoidance to test associative memory and other tasks such as hot-plate sensitivity, exploratory locomotor activity by the open field actimeter [40]. Associative short- and long-term memories were determined by novel object recognition (NOR) task as described [41].…”

Developmental control of noradrenergic system by SLITRK1 and its implications in the pathophysiology of neuropsychiatric disorders

“…Clonidine administration during P8–P21 (P8, 8 μg/kg; P9, 25 μg/kg, twice a day, subcutaneous, 100 μg/kg) reduced rapid eye movement sleep during P8–P21 and increased locomotor activity at the adult stage (>P70; Mirmiran et al, 1983 ). In mice, clonidine treatment during the P1–P22 period (daily, subcutaneous, 35 μg/kg) resulted in a temporal delay in the appearance of developmental markers (surface righting, cliff aversion, rooting, pinna detachment, startle response, eye twitch, eye opening), reduced exploratory locomotor activity at P16, and impaired short-term memory in the novel object recognition task at P22 ( Calvino-Núñez and Domínguez-del-Toro, 2014 ).…”