Effect of Ventromedial and Dorsomedial Hypothalamic Lesions on Circadian Corticosterone Rhythms

Bellinger, Larry L.; Bernardis, Lee L.; Mendel, V. E.

doi:10.1159/000122628

Cited by 81 publications

(31 citation statements)

References 12 publications

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“…Food intake is decreased at night; however, body weight, insulin, leptin, and fat depot weights do not change. These results agree well with those of Bellinger and Bernardis (14,30,31), who show that lesions of the DMN in weanling rats result in small adults that eat less but strictly in proportion to body weight, and thus have normal body composition. Our other studies (submitted) show that rats with DMN disruption are more sensitive than sham-disrupted rats to the effects of intracerebroventricularly administered leptin, suggesting that the DMN normally abrogate, to some extent, the dominant inhibitory effects of leptin, and possibly other signals of energy stores, on food intake.…”

Section: Discussionsupporting

confidence: 92%

“…Refs. 11,13,14).Because all four of the medial hypothalamic cell groups have been implicated in the regulation of energy balance (15), reported to contain leptin receptors (16,17), and strongly interconnected (18 -22), it is important to distinguish among them, if possible, to learn more about functions in each nucleus.We used small injections of colchicine (23) to inhibit function in each of four medial hypothalamic cell groups so that we could determine the specific effects of inhibition in a given cell group on food intake, hormones, and fat stores. Previous studies using colchicine as a reversible neurotoxin have shown acute responses that are identical to those of irreversible excitotoxin lesions (23,24).…”

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confidence: 99%

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Hypothalamic Obesity: Multiple Routes Mediated by Loss of Function in Medial Cell Groups1

Choi

Dallman

1999

Endocrinology

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Cell groups of the medial hypothalamus are key to the regulation of energy balance. Functional disruption by colchicine injected in the hypothalamic arcuate (ARC), paraventricular (PVN), and ventromedial (VMN) cell groups produced increased food intake and obesity; disruption of the dorsomedial nuclei (DMN) produced decreased food intake. Colchicine in ARC or PVN increased food intake during both light and dark periods and increased cumulative food intake. By contrast, colchicine in VMN increased food intake only during the light, and cumulative food intake was not increased. Both leptin and insulin were elevated in the obese rats. Compared with sham, the slope of regression of leptin on insulin was increased by disruption of PVN and DMN but was not altered by disruption of VMN. ARC disruption abolished the relationship between leptin and insulin. Colchicine injected in the DMN did not cause obesity but altered feeding and the normal relationship between leptin, fat, and insulin, suggesting that blockade of signals, for example, from the lateral hypothalamus to DMN may disinhibit the normal medial hypothalamic drive to decrease energy stores. Changes in caloric efficiency with time after colchicine injections suggest that rats with both ARC and PVN disruption respond to signals of obesity, whereas rats with VMN disruption do not. These studies distinguish among functions in the four medial hypothalamic nuclei and suggest that interactions among them normally serve to regulate energy balance through alterations in food acquisition and storage. (Endocrinology 140: [4081][4082][4083][4084][4085][4086][4087][4088] 1999) C RITICAL to understanding the etiology of obesity is detailing the processes that occur after initiation of the obesity-stimulating event. To date, this has not been possible with genetic obesities because site-specific, conditional gene knockouts have not yet been produced. Comparison of the obesity after disruption of the melanocortin system to that after disruption of the leptin system suggests that these are produced by different mechanisms. A recent study has shown that crossing agouti (A y /a)with leptin deficient ob/ob mice causes independent and additive obesities (1), showing that both types of genetic obesity implicate abnormal activity in medial hypothalamic nuclei for their phenotypic expression and that these genetic obesities are caused by different mechanisms.Antagonism by the agouti peptide or deletion of the melanocortin 4-receptor (MC4-R) results in obesity probably as a consequence of abnormal function of the MC4-R on neurons in the dorsomedial nuclei (DMN) and paraventricular nuclei (PVN), which are innervated by melanocortin-producing, POMC-expressing cells in the arcuate nuclei (ARC) (2). Neonatal treatment of rats with monosodium glutamate results in obese adults with reduced numbers of POMC neurons (3). Study of the ob/ob, db/db, and fa/fa phenotypes (the latter two lack leptin receptors) shows that abnormal leptin signaling results in elevated neuropeptide Y (NPY)...

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Section: Discussionsupporting

confidence: 92%

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confidence: 99%

Hypothalamic Obesity: Multiple Routes Mediated by Loss of Function in Medial Cell Groups1

Choi

Dallman

1999

Endocrinology

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“…Lesions of the VMH, but not the suprachiasmatic nucleus, abolish this change in circadian corticosterone levels in food restricted rats (50,51). Additionally, lesions or inhibition of the VMH alter diurnal corticosterone rhythms (54)(55)(56). These findings suggest that the VMH may be critical in linking nutritional status into circadian neuroendocrine responses.…”

Section: Discussionmentioning

confidence: 89%

Leptin activates distinct projections from the dorsomedial and ventromedial hypothalamic nuclei

Elmquist

Ahima

Elias

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

341

221

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Leptin has profound effects on feeding, metabolism, and neuroendocrine status. Evidence indicates that the hypothalamus coordinates these responses, though the specific brain pathways engaged by leptin remain obscure. The paraventricular nucleus of the hypothalamus (PVH) regulates pituitary gland function and feeding, and innervates autonomic preganglionic neurons, making it a candidate to regulate many of the responses to leptin. The subparaventricular zone, an anterior hypothalamic region receiving dense innervation from the suprachiasmatic nucleus, is thought to integrate circadian and metabolic information. We investigated the distribution of neurons in the rat brain activated by leptin administration that also project to the PVH or the subparaventricular zone by coupling immunohistochemistry for Fos with retrograde transport of cholera toxin-b. Intravenous leptin characteristically activated several cell groups including the ventromedial hypothalamic nucleus, the dorsomedial hypothalamic nucleus (DMH), and the PVH. When tracer injections were centered in the subparaventricular zone, many double-labeled cells were observed in the dorsomedial subdivision of the ventromedial hypothalamic nucleus. This projection may provide an anatomic substrate for integration of metabolic and circadian information to regulate the hypothalamo-pituitary axis. When cholera toxin-b injections were centered in the PVH, many double-labeled cells were found within the caudal DMH. Hence, activation of specific neuroendocrine and autonomic elements of the PVH may be triggered by leptin-activated afferents arising in the DMH. Our results demonstrate that a discrete set of hypothalamic pathways may underlie leptin's autonomic, endocrine, and behavioral effects.

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“…Furthermore, VMH lesions interfere with the diurnal rhythms of plasma corticosterone levels and food intake (Balagura and Devenport, 1970;Bellinger et al, 1976;Bernardis, 1973). There is also general agreement that the VMH plays important roles in the regulation of feeding (Brooks et al, 1946;Minano and Myers, 1991;Perkins et al, 1981;Shimizu et al, 1987), defensive (Fuchs et al, 1985a;, and feminine copulatory behaviors and the modulation of autonomic responses associated with these behaviors.…”

Section: From a Neuroendocrine Aspect It Is Interesting To Note Thatmentioning

confidence: 99%

Distribution of type 1 cannabinoid receptor‐expressing neurons in the septal‐hypothalamic region of the mouse: Colocalization with GABAergic and glutamatergic markers

Hrabovszky

Wittmann

Kalló

et al. 2012

J of Comparative Neurology

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Type 1 cannabinoid receptor (CB1) is the principal mediator of retrograde endocannabinoid signaling in the brain. In this study, we addressed the topographic distribution and amino acid neurotransmitter phenotype of endocannabinoid‐sensitive hypothalamic neurons in mice. The in situ hybridization detection of CB1 mRNA revealed high levels of expression in the medial septum (MS) and the diagonal band of Broca (DBB), moderate levels in the preoptic area and the hypothalamic lateroanterior (LA), paraventricular (Pa), ventromedial (VMH), lateral mammillary (LM), and ventral premammillary (PMV) nuclei, and low levels in many other hypothalamic regions including the suprachiasmatic (SCh) and arcuate (Arc) nuclei. This regional distribution pattern was compared with location of γ‐aminobutyric acid (GABA)ergic and glutamatergic cell groups, as identified by the expression of glutamic acid decarboxylase 65 (GAD65) and type 2 vesicular glutamate transporter (VGLUT2) mRNAs, respectively. The MS, DBB, and preoptic area showed overlaps between GABAergic and CB1‐expressing neurons, whereas hypothalamic sites with moderate CB1 signals, including the LA, Pa, VMH, LM, and PMV, were dominated by glutamatergic neurons. Low CB1 mRNA levels were also present in other glutamatergic and GABAergic regions. Dual‐label in situ hybridization experiments confirmed the cellular co‐expression of CB1 with both glutamatergic and GABAergic markers. In this report we provide a detailed anatomical map of hypothalamic glutamatergic and GABAergic systems whose neurotransmitter release is controlled by retrograde endocannabinoid signaling from hypothalamic and extrahypothalamic target neurons. This neuroanatomical information contributes to an understanding of the role that the endocannabinoid system plays in the regulation of endocrine and metabolic functions. J. Comp. Neurol. 520:1005–1020, 2012. © 2011 Wiley Periodicals, Inc.

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Effect of Ventromedial and Dorsomedial Hypothalamic Lesions on Circadian Corticosterone Rhythms

Cited by 81 publications

References 12 publications

Hypothalamic Obesity: Multiple Routes Mediated by Loss of Function in Medial Cell Groups1

Hypothalamic Obesity: Multiple Routes Mediated by Loss of Function in Medial Cell Groups1

Leptin activates distinct projections from the dorsomedial and ventromedial hypothalamic nuclei

Distribution of type 1 cannabinoid receptor‐expressing neurons in the septal‐hypothalamic region of the mouse: Colocalization with GABAergic and glutamatergic markers

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