Effects Of Hypothalamic Lesions Research Articles

BDNF levels in adipose tissue and hypothalamus were reduced in mice with MSG-induced obesity

Objectives: To observe the expression of brain-derived neurotrophic factor (BDNF) in hypothalamic and adipose tissue in mice with monosodium glutamate (MSG)-induced obesity.Methods: The effects of hypothalamic lesions, specifically arcuate nucleus (ARC) lesions, induced by MSG injection were studied in male ICR mice at the neonatal stage. The following parameters were compared: body weight, body length, Lee's index, food intake, body temperature, fat weight, and levels of total cholesterol (CHOL), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and blood glucose (GLU). The BDNF expression levels in hypothalamic and adipose tissue were measured using western blotting.Results: Compared with the control group, the model group body had significantly higher weight, Lee's index, food intake, fat weight, CHOL, TG, LDL, HDL, and GLU levels. BDNF expression levels in hypothalamic and adipose tissue were markedly down-regulated in the model group.Discussion: BDNF may be closely associated with MSG-induced hypothalamic obesity.

The Effect of Hypothalamic Lesions on Hypothalamo-Pituitary-Adrenal Axis Activity and Inflammation in Adjuvant-Induced Arthritis

Adjuvant-induced arthritis (AA) was induced in control and in hypothalamic lesioned Piebald-Viral-Glaxo (PVG) rats. Following discrete paraventricular nucleus (PVN) lesions plasma corticosterone was increased 14 days after adjuvant injection as in controls, when hind paw inflammation was apparent. PVN lesion did not affect the severity of inflammation. In contrast, following medial basal hypothalamus (MBH) lesions adjuvant did not increase corticosterone levels and the increase in paw volume at day 14 was potentiated. Basal proopiomelanocortin (POMC) mRNA expression in the anterior lobe was unchanged by PVN lesions and decreased by MBH lesions. AA increased POMC mRNA in controls and in both PVN and MBH lesioned rats. After complete MBH lesion, surviving anterior pituitary tissue maintained morning levels of corticosterone.Thus, AA may activate the hypothalamo-pituitary-adrenal axis without the mediation of PVN neurones projecting to the median eminence. However, the loss of the corticosterone response to AA and the increase in severity of inflammation in the MBH lesioned rats suggests a central (non-PVN) component mediates effects of inflammation. Furthermore, the increase in POMC mRNA in the MBH lesioned AA rats suggests that part of this process is not mediated by releasing factors in the hypothalamo-hypophysial portal system, and that extrahypothalamic (peripheral) mediators act on the pituitary during chronic inflammation.

Effect of hypothalamic lesion or chemical axotomy on restitution of immunoreactivity in mice after cyclophosphamide administration

Splenocytes harvested from mice that underwent chemical axotomy (by 6-hydroxydopamine) or that had electric lesions in their anterior hypothalami demonstrated a significant decrease in their proliferative ability after concanavalin-A stimulation in vitro. In axotomized mice pre-treated with cyclophosphamide, faster restitution of the proliferative activity was observed on days 6–8 after the drug's administration. Splenocytes isolated from mice treated with 6-hydroxydopamine did not exhibit any suppressive activity, which is characteristic of the restitution period following administration of cyclophosphamide. These results indicate that the autonomic nervous system exert a direct effect on immunoreactivity and on processes which are responsible for restitution after cyclophosphamide-induced immunodisorders.

Effects of hypothalamic lesions on the body temperature rhythm of the golden hamster.

The effects of electrolytic and neurotoxic lesions of the suprachiasmatic nucleus (SCN) and preoptic area (POA) of the anterior hypothalamus were studied by temperature telemetry in the golden hamster (Mesocricetus auratus) examined under two ambient temperature conditions: 24 degrees C and 6 degrees C. Although attempted lesions with microinjections of ibotenic acid proved unsuccessful, electrolytic lesions of the SCN eliminated the circadian rhythm of body temperature (CRT), indicating an active role of this nucleus in the establishment of the CRT. Electrolytic lesions of the POA, but not of the SCN, resulted in an increased amplitude of the CRT at both 24 degrees C and 6 degrees C, with the lower ambient temperature enhancing this amplitude change to a greater extent. These results suggest that the POA and the SCN are independently responsible for the homeostatic and circadian regulation of body temperature, respectively. The increased amplitude of the CRT after POA lesions raises the possibility that the thermoregulatory system may oppose rather than defend the circadian control of body temperature in normal animals, which is consistent with several recent behavioral findings.

Perioperative Thermoregulatory Dysfunction in a Patient with a Previous Traumatic Hypothalamic Injury

Perioperative Thermoregulatory Dysfunction in a Patient with a Previous Traumatic Hypothalamic Injury

Effects of hypothalamic lesions on stress-induced hypocalcemia, gastric ulcers and emotional behaviors in rats

Effects of hypothalamic lesions on stress-induced hypocalcemia, gastric ulcers and emotional behaviors in rats

Facilitation of liver regeneration after partial hepatectomy by ventromedial hypothalamic lesions in rats.

Whether or not the hypothalamus is involved in initiating hepatic DNA synthesis after partial hepatectomy is unclear. To determine the role of the ventromedial hypothalamic nuclei in liver regeneration after partial hepatectomy, we studied hepatic DNA synthesis during liver regeneration in rats with bilateral lesions of these nuclei. Lesions of the ventromedial hypothalamus accelerated the increase in hepatic DNA synthesis and raised the peak level of thymidine incorporation after partial hepatectomy. These effects of hypothalamic lesions were completely inhibited by hepatic vagotomy. Thus, lesions of the ventromedial hypothalamus appear to promote hepatic regeneration by increasing vagal stimulation of the liver.

Hypothalamic linkage in stress-induced hypocalcemia, gastric damage, and emotional behavior in rats.

The effects of hypothalamic lesions on stress-induced hypocalcemia, gastric damage, and swim test-evoked behavior were examined in rats. Bilateral lesions of the ventromedial nucleus in the hypothalamus (VMH) eliminated water-restraint stress-induced hypocalcemia and attenuated any gastric damage compared with those in the sham-operated rats. In contrast, lesions in the paraventricular nucleus (PVN) exacerbated both the stress-induced hypocalcemia and gastric lesions in comparison with those in the control rats. In a forced-swimming test, the VMH-lesioned rats showed a significantly shorter time of immobility as well as a longer duration of struggling than the control rats, respectively, while the PVN-lesioned animals spent a longer time in immobility and a shorter period struggling than the control rats. These results suggest that the VMH has an accelerative action in stress-induced hypocalcemia, gastric lesions, and behavioral despair, while the PVN has an opposite effect.

Effects of hypothalamic lesions on courtship and copulatory behavior in sexual and unisexual whiptail lizards

Lesions of the anterior hypothalamus-medial preoptic area (AH-MPOA) impair courtship and copulatory behavior in male Cnemidophorus inornatus, a sexually reproducing species of whiptail lizard, and male-like pseudosexual behaviors in C. uniparens, an all-female species. These results suggest that, since C. inornatus is a direct ancestor to C. uniparens, the neural structures responsible for mediating male-typical courtship and copulatory behavior in male whiptails are conserved in the evolution of the all-female parthenogen.

Effect of hypothalamic lesions on interaction of centrally administered ANF and the circulating sodium-pump inhibitor.

We investigated the possible central interaction of atrial natriuretic factor (ANF) and an endogenous Na+, K(+)-ATPase (Na-pump) inhibitor in normal rats. Release of an endogenous Na-pump inhibitor associated with deoxycorticosterone acetate-salt hypertension may be regulated in the anteroventral third ventricle (AV3V) area of the CNS. We reported earlier that bolus injection of synthetic 26-amino acid ANF (Arg101-Tyr126, 6 micrograms/250 g rat) into the lateral brain ventricle (ICV) promotes the appearance in the plasma of a Na-pump inhibitor in rats. To determine whether the AV3V area of the brain is involved in the ICV effect of ANF, we introduced electrolytic lesions in this area. This treatment abolished the appearance of the Na-pump inhibitor after intraventricular injection of ANF. To further localize the area and the pathways involved in the interaction of ANF and the Na-pump inhibitor, we produced bilateral medial coronal knife cuts designed to transect the medially coursing pathway through the periventricular tissue of the AV3V region between the level of the medial preoptic area and the anterior hypothalamic nuclei. These knife cuts also abolished the appearance of the Na-pump inhibitor after ICV injection of ANF. Our data to date indicate that centrally administered ANF promotes the appearance of a Na-pump inhibitor in the plasma. A central site of interaction between ANF and the Na-pump inhibitor appears to be the AV3V area and a medial pathway coursing caudally from the AV3V region.

Effect of hypothalamic lesions that induce precocious puberty on the morphological and functional maturation of the luteinizing hormone-releasing hormone neuronal system.

Recent evidence has implicated the transforming growth factor-alpha (TGF alpha)/epidermal growth factor receptor (EGFR) system in the mechanism by which hypothalamic lesions accelerate female sexual development. Since acquisition and maintenance of reproductive functions depend on the secretory activity of LHRH neurons, the present studies were undertaken to characterize some of the cellular and molecular events that underlie lesion-induced activation of the LHRH neuronal network. Bilateral electrolytic lesions of the posterior portion of the preoptic region and anterior hypothalamic area (POA-AHA) in 22-day-old rats resulted in vaginal opening and ovulation within 7 days. Morphological maturation of LHRH neurons was assessed by the relative frequency of irregular and smooth neurons (the former being the predominant type in adult animals). Within 20 h after the lesion, there was a significant decrease in the proportion of LHRH neurons with spiny irregular contours, indicating reversal to a more immature morphological type. This change was followed by accelerated spine reformation, so that at the time of precocious proestrus, the incidence of irregular LHRH neurons was similar in lesioned and age-matched control rats. A striking increase in c-fos mRNA levels occurred within 1 h after the lesion in the area neighboring the site of injury, reflecting the immediate cell response to trauma. Immunohistochemical localization of the c-fos protein, used to estimate changes in cellular activity at the single cell level, demonstrated c-fos induction in unidentified cells near the lesion and astrocytes, but not in LHRH neurons 20 h after injury. In contrast, a selective increase in c-fos expression was observed in LHRH neurons during the initiation of precocious puberty 5-7 days later at the time of the first proestrus. An increase in plasma LH associated with a drop in LHRH content in the median eminence and an increase in pro-LHRH precursor in the POA-AHA, with no changes in LHRH mRNA, was found to antedate the first preovulatory surge of gonadotropins in lesioned rats. Assessment of the changes in PC2 mRNA, which encodes a novel dibasic endoprotease presumptively involved in tissue-specific processing of a class of prohormones that includes pro-LHRH, showed that the content of PC2 mRNA in the AHA-POA increases during normal puberty, but not in lesioned animals, thus providing a potential explanation for the divergent changes in pro-LHRH and mature decapeptide found in lesioned rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of hypothalamic lesions that induce precocious puberty on the morphological and functional maturation of the luteinizing hormone- releasing hormone neuronal system

Effect of hypothalamic lesions that induce precocious puberty on the morphological and functional maturation of the luteinizing hormone- releasing hormone neuronal system

The effect of hypothalamic lesions on the length of gestation in fetal sheep

Twenty-nine sheep fetuses were subject to stereotaxic surgery at 106 to 110 days of gestation. Electrolytic lesions were placed bilaterally in the anterior hypothalamus. Sham-operated controls (n = 4) were delivered at 146.3 +/- 4.3 days. Of the fetuses with lesions, two were excluded because histologic confirmation of the lesion was not possible. Those fetuses with bilateral lesions of the suprachiasmatic nuclei (n = 4) were delivered at 148 +/- 10 days. In 10 animals with bilateral lesions of the paraventricular nuclei, delivery was significantly (p less than 0.0001) prolonged to at least 165.6 +/- 5.1 days. In nine animals with lesions not involving the endocrine hypothalamus, delivery was at 148.1 +/- 4.3 days. All animals that were delivered after 157 days (n = 9) had lesions including the paraventricular nuclei bilaterally (p less than 0.01). The adrenal glands of fetuses with prolonged gestation were normal in weight and light microscopic appearance. These observations demonstrate that fetal neural pathways involving the paraventricular nuclei are essential for parturition in the sheep. However, fetal adrenal growth can continue without such influences.

The effect of hypothalamic lesions on the length of gestation in fetal sheep

Twenty-nine sheep fetuses were subject to stereotaxic surgery at 106 to 110 days of gestation. Electrolytic lesions were placed bilaterally in the anterior hypothalamus. Sham-operated controls (n = 4) were delivered at 146.3 ± 4.3 days. Of the fetuses with lesions, two were excluded because histologic confirmation of the lesion was not possible. Those fetuses with bilateral lesions of the suprachiasmatic nuclei (n = 4) were delivered at 148 ± 10 days. In 10 animals with bilateral lesions of the paraventricular nuclei, delivery was significantly (p<0.0001) prolonged to at least 165.6 ± 5.1 days. In nine animals with lesions not involving the endocrine hypothalamus, delivery was at 148.1 ± 4.3 days. All animals that were delivered after 157 days (n = 9) had lesions including the paraventricular nuclei bilaterally (p<0.01). The adrenal glands of fetuses with prolonged gestation were normal in weight and light microscopic appearance. These observations demonstrate that fetal neural pathways involving the paraventricular nuclei are essential for parturition in the sheep. However, fetal adrenal growth can continue without such influences. Twenty-nine sheep fetuses were subject to stereotaxic surgery at 106 to 110 days of gestation. Electrolytic lesions were placed bilaterally in the anterior hypothalamus. Sham-operated controls (n = 4) were delivered at 146.3 ± 4.3 days. Of the fetuses with lesions, two were excluded because histologic confirmation of the lesion was not possible. Those fetuses with bilateral lesions of the suprachiasmatic nuclei (n = 4) were delivered at 148 ± 10 days. In 10 animals with bilateral lesions of the paraventricular nuclei, delivery was significantly (p<0.0001) prolonged to at least 165.6 ± 5.1 days. In nine animals with lesions not involving the endocrine hypothalamus, delivery was at 148.1 ± 4.3 days. All animals that were delivered after 157 days (n = 9) had lesions including the paraventricular nuclei bilaterally (p<0.01). The adrenal glands of fetuses with prolonged gestation were normal in weight and light microscopic appearance. These observations demonstrate that fetal neural pathways involving the paraventricular nuclei are essential for parturition in the sheep. However, fetal adrenal growth can continue without such influences.

Adipocyte Dynamics in Hypothalamic Obese Mice during Food Deprivation and Refeeding.

Effect of hypothalamic lesions on regulation of body weight and fat cell dynamics in obese mice were examined during refeeding after prolonged food deprivation. Obese mice, which were treated with monosodium glutamate for 5 postnatal days and had ventromedial nuclear lesions in the hypothalamus, were used. When adult obese mice were given a glucose electrolyte solution for 20-40 days, the body weight dropped to about 45% of their pre-treatment weight. After reinstituted feeding of normal mouse food ad libitum, their body weight and adipose tissue weight returned to pre-starvation level. Tritiated thymidine autoradiography revealed that cell proliferation occurred in the early stages of refeeding and some fat cells were renewed in the epididymal adipose tissue. Fat cell renewal was found more active in the experimental group than in the control. Thereafter, fat cell size increased gradually via fat storage. These obese mice were found to have the capacity to regulate their body weight and adipose tissue not only through fat storage but also by increasing number of fat cells, in order to replace the cells which were lost during starvation. Therefore, ventromedial nuclear lesion in the hypothalamus does not influence the regulatory mechanism of adipose tissue during starvation and refeeding.

Differential Elimination of Circadian and Ultradian Rhythmicity by Hypothalamic Lesions in the Common Vole, Microtus arvalis

Effects of hypothalamic lesions on the ultradian and circadian organization of wheel running and feeding were studied in the common vole, Microtus arvalis. Circadian organization broke down within 30 days in continuous darkness in 24% of intact voles (n = 135). Ultradian rhythmicity of feeding (period 2-3 hr) persisted in constant conditions in all intact voles. Following lesions of the suprachiasmatic nuclei (SCN), circadian rhythmicity disappeared when lesions were complete (n = 8) or more extensive than 25% of the total SCN volume (n = 5). Absence of circadian rhythmicity was also found in animals with substantial lesions in the diencephalic paraventricular area (PVA) and in the retrochiasmatic area (RCA) and/or adjacent arcuate nucleus (Arc). Complete loss of ultradian and circadian organization occurred in eight voles with damage to the RCA and/or Arc. In three of these, the SCN was intact. The SCN is a likely candidate for a circadian pacemaker in voles (as in other rodents), while the loss of circadian rhythmicity following PVA and RCA/Arc lesions may be due to destruction of efferent pathways from the SCN. The RCA/Arc area is apparently necessary for the expression of ultradian rhythms. The intact SCN is neither necessary nor sufficient for the generation of ultradian rhythmicity.

Effects of hypothalamic lesions on temperature regulation in pigeons

The effect of hypothalamic lesions on temperature regulation was studied in pigeons by recording deep and skin temperatures, shivering, panting and oxygen consumption. Thresholds of shivering and panting were assessed before and after lesions. Survival was 100% when lesions were done in awake animals in a cool environment. Lesions anterior to the anterior commissure which included the preoptic area resulted in an increased threshold of panting or a lack of panting response at body temperatures up to 44.5°C. Shivering response was unchanged in these animals. Lesions posterior to the anterior commissure were followed by a lack of shivering response with no change in panting threshold. This points to a segregation of the hypothalamic structures controlling heat loss and heat gain in the pigeon.

Effects of hypothalamic lesions upon the sexual and social behaviour of the male common marmoset ( Callithrix jacchus)

The sexual and associated behaviour of 10 adult male marmosets was recorded during pair tests with ovariectomized females, before and after bilateral thermal lesions of the hypothalamus. Four sham-lesioned males served as controls. Lesions varied in volume from 1.49 to 3.28 mm 3 and extended from the ventromedial hypothalamus to the diagonal band of Broca. Precpulatory behaviours (anticipatory erections, tongue flicking and anogenital investigations of the female) as well as frequencies of mounting, intromission and ejaculation decreased in lesioned males. The greatest suppression of sexual behaviour occurred after lesioning the anterior hypothalamus (AH), beneath the anterior commissure, or at the junction of the AH with the preoptic area (POA). Lesions confined to the POA had less profound behavioural effects. Treating ovariectomized females with estradiol stimulated their proceptivity but had no consistent effects upon the male's behaviour. Lesioned males did not exhibit signs of social withdrawal and frequencies of allogrooming or grooming invitations increased post-operatively. Preliminary studies on intermale aggression indicated that lesions which had he greatest effect upon sexual behaviour also tended to decrease aggressive interaction with other males. Hypothalamic lesions did not affect plasma testosterone levels, except in one male and only one animal showed signs pf ill health (weight loss and hypothemia) post-operatively. These results show that damage to the AH or AH-POA junction in male marmosets causes a profound suppression of sexual ‘arousal’ and copulatory behavior and that such affects are not due to androgen insufficiency or other, non-specific, side effects of neural damage.

Hypothalamus and sodium-potassium pump activity in skeletal muscles of DOCA-hypertensive rats.

The effects of hypothalamic lesions on Na+ and K+ content ([Na+]i and [K+]i) in both slow tonic muscle [soleus (SOL)] and fast-twitch muscle [extensor digitorum longus (EDL)] were investigated in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. In DOCA-treated rats, [Na+]i was increased and [K+]i decreased in both SOL and EDL muscles compared with controls. Cellular K+ loss and Na+ accumulation in SOL were restored after tibial nerve sectioning (delta [Na+]i, -14.2 +/- 2.6 and delta [K+]i, 13.9 +/- 2.6 mmol/l fiber water (FW), n = 18, P less than 0.01) or bilateral lesioning of the ventromedial hypothalamic nucleus (VMH) (delta [Na+]i, -15.5 +/- 1.5 and delta [K+]i, 17.4 +/- 4.6 mmol/l FW, n = 6, P less than 0.01 and P less than 0.05). On the other hand, the anomalous electrolyte content in EDL was counteracted by lesions of anteroventral portion of the third ventricle (AV3V) (delta [Na+]i, -8.8 +/- 1.6 and delta [K+]i, 5.2 +/- 1.2 mmol/l FW, n = 6, P less than 0.01 and P less than 0.05) or paraventricular hypothalamic nucleus (PVN) (delta [Na+]i, -6.8 +/- 0.6 and 5.7 +/- 1.2 mmol/l FW, n = 6, P less than 0.01 and P less than 0.05), but aggravated by denervation (delta [Na+]i, 13.4 +/- 1.8 and delta [K+]i, -9.6 +/- 1.8 mmol/l FW, n = 18, P less than 0.01). These results suggest that there are at least two hypothalamic mechanisms of suppression of muscle Na-K pump activity in DOCA-hypertensive rats; i.e., neurally mediated inhibition in SOL by the VMH and, presumably, humorally mediated inhibition originating from the AV3V or PVN with greater influence in EDL.

Effects of hypothalamic lesions on lymphocyte subsets in mice.

This study investigated the time course of the dynamics of lymphocyte subsets in the peripheral blood of mice, after bilateral lesions were made at anterior, middle and posterior sites in the hypothalamus of the mice, using a stereotaxic technique. Lymphocyte subsets were analyzed by using monoclonal antibodies specific to cell surface markers and a laser flow cytometry system. The results indicate that the anterior and posterior parts of the hypothalamus seem to play a role in immunomodulation of both helper and suppressor T lymphocytes. The middle part of the hypothalamus is considered to be the site of a control mechanism in the immune regulation of T and B lymphocytes.