Rat Brain Nuclei Research Articles

Cannabinoid Receptors CB1 and CB2 Form Functional Heteromers in Brain

Exploring the role of cannabinoid CB(2) receptors in the brain, we present evidence of CB(2) receptor molecular and functional interaction with cannabinoid CB(1) receptors. Using biophysical and biochemical approaches, we discovered that CB(2) receptors can form heteromers with CB(1) receptors in transfected neuronal cells and in rat brain pineal gland, nucleus accumbens, and globus pallidus. Within CB(1)-CB(2) receptor heteromers expressed in a neuronal cell model, agonist co-activation of CB(1) and CB(2) receptors resulted in a negative cross-talk in Akt phosphorylation and neurite outgrowth. Moreover, one specific characteristic of CB(1)-CB(2) receptor heteromers consists of both the ability of CB(1) receptor antagonists to block the effect of CB(2) receptor agonists and, conversely, the ability of CB(2) receptor antagonists to block the effect of CB(1) receptor agonists, showing a bidirectional cross-antagonism phenomenon. Taken together, these data illuminate the mechanism by which CB(2) receptors can negatively modulate CB(1) receptor function.

Anatomically‐Specific Actions of Oestrogen Receptor in the Developing Female Rat Brain: Effects of Oestradiol and Selective Oestrogen Receptor Modulators on Progestin Receptor Expression

Steroid hormones largely exert their actions by activating nuclear receptors, which, as transcription factors, powerfully influence fundamental processes of neural development. Often, steroid receptor action demonstrates remarkable specificity under different developmental, anatomical or hormonal conditions. Yet, the mechanisms underlying such specificity are poorly understood. The present study examined the anatomically-specific regulation of progestin receptor (PR) expression by oestrogen receptor (ER) activation in the ventromedial nucleus (VMN) of the hypothalamus and the medial preoptic nucleus (MPN) of the neonatal female rat brain, using the selective oestrogen receptor modulators (SERMs), tamoxifen and ICI 182780 (ICI), in the presence or absence of oestradiol benzoate (EB) treatment. The results demonstrate that PR immunoreactivity (PR-ir) in the neonatal female MPN was significantly increased by EB and this increase was abolished by either tamoxifen or ICI treatment. In contrast, within the VMN of the same animals, EB had no effect on PR-ir and the SERMs only modestly decreased PR-ir. Interestingly, ICI acted as a true antagonist regardless of EB treatment, whereas tamoxifen acted as an ER agonist in the absence of EB in the MPN, but not the VMN, representing one of the first in vivo demonstrations of tissue-specific and oestradiol-independent effects of tamoxifen on ER activation. The present results indicate that PR expression is highly dependent on oestradiol and its receptor in the MPN, although it is independent of both oestradiol and ER activation within the neonatal VMN. These findings demonstrate the anatomically-specific actions of oestradiol and its receptor to induce PR in two brain regions controlling different aspects of female reproductive behaviours in adulthood.

Paul Greengard: Signals underlying moods, addictions, and brain disorders

Although certain neurotransmitters had been identified more than 40 years ago, scientists knew relatively little about how these chemicals actually functioned. The basis for much of what neuroscientists know today about brain signaling was shaped by National Academy of Sciences member Paul Greengard's 1972 PNAS Classic paper, “Dopamine-sensitive Adenylate cyclase in caudate nucleus of rat brain, and its similarity to the ‘dopamine receptor’” (1).

Nigriventrine: A low molecular mass neuroactive compound from the venom of the spider Phoneutria nigriventer

Nigriventrine was isolated from the “armed” spider Phoneutria nigriventer, in which it constitutes about 0.4% of the total venom content. Its structure was determined to be [1,1′-(1-hydroxyhydrazine-1,2-diyl)bis(oxy)bis(4-hydroxy-2,6-dioxopiperidine-4 carboxylic acid)] by NMR, HR-ES/IMS and MS/MS methods. The intracerebroventricular application of nigriventrine in rat brain, followed by the detection of c-Fos protein expression, indicated that the compound was neuroactive in the motor cortex, sensory cortex, piriform cortex, median preoptic nucleus, dorsal endopiriform nucleus, lateral septal nucleus and hippocampus of rat brain. Nigriventrine causes convulsions in rats, even when peripherally applied.

Organization of amyloid-beta protein precursor intracellular domain-associated protein-1 in the rat brain.

Sustained activity-dependent synaptic modifications require protein synthesis. Although proteins can be synthesized locally in dendrites, long-term changes also require nuclear signaling. Amyloid-beta protein precursor intracellular domain-associated protein-1 (AIDA-1), an abundant component of the biochemical postsynaptic density fraction, contains a nuclear localization sequence, making it a plausible candidate for synapse-to-nucleus signaling. We used immunohistochemistry to study the regional, cellular, and subcellular distribution of AIDA-1. Immunostaining was prominent in the hippocampus, cerebral cortex, and neostriatum. Along with diffuse staining of neuropil, fluorescence microscopy revealed immunostaining of excitatory synapses throughout the forebrain, and immunoreactive puncta within and directly outside the nucleus. Presynaptic staining was conspicuous in hippocampal mossy fibers. Electron microscopic analysis of material processed for postembedding immunogold revealed AIDA-1 label within postsynaptic densities in both hippocampus and cortex. Together with previous work, these data suggest that AIDA-1 serves as a direct signaling link between synapses and the nucleus in adult rat brain.

Abdominal surgery activates nesfatin-1 immunoreactive brain nuclei in rats

Abdominal surgery-induced postoperative gastric ileus is well established to induce Fos expression in specific brain nuclei in rats within 2-h after surgery. However, the phenotype of activated neurons has not been thoroughly characterized. Nesfatin-1 was recently discovered in the rat hypothalamus as a new anorexigenic peptide that also inhibits gastric emptying and is widely distributed in rat brain autonomic nuclei suggesting an involvement in stress responses. Therefore, we investigated whether abdominal surgery activates nesfatin-1-immunoreactive (ir) neurons in the rat brain. Two hours after abdominal surgery with cecal palpation under short isoflurane anesthesia or anesthesia alone, rats were transcardially perfused and brains processed for double immunohistochemical labeling of Fos and nesfatin-1. Abdominal surgery, compared to anesthesia alone, induced Fos expression in neurons of the supraoptic nucleus (SON), paraventricular nucleus (PVN), locus coeruleus (LC), Edinger-Westphal nucleus (EW), rostral raphe pallidus (rRPa), nucleus of the solitary tract (NTS) and ventrolateral medulla (VLM). Double Fos/nesfatin-1 labeling showed that of the activated cells, 99% were nesfatin-1-immunoreactive in the SON, 91% in the LC, 82% in the rRPa, 74% in the EW and VLM, 71% in the anterior parvicellular PVN, 47% in the lateral magnocellular PVN, 41% in the medial magnocellular PVN, 14% in the NTS and 9% in the medial parvicellular PVN. These data established nesfatin-1 immunoreactive neurons in specific nuclei of the hypothalamus and brainstem as part of the neuronal response to abdominal surgery and suggest a possible implication of nesfatin-1 in the alterations of food intake and gastric transit associated with such a stressor.

Adeno-associated viral vector (AAV)-mediated gene transfer in the red nucleus of the adult rat brain: Comparative analysis of the transduction properties of seven AAV serotypes and lentiviral vectors

Recombinant adeno-associated viral vectors (AAVs) are very promising gene transfer tools for the nervous system. We have compared the efficiency of gene expression of seven AAV serotypes in young adult rats following a single injection in a major nucleus of the mid brain, the red nucleus, which is the origin of the rubrospinal tract. AAV serotypes 1–6 and 8 and a lentiviral vector (LV) were used, all encoding green fluorescent protein (GFP) under control of the cytomegalovirus (CMV) promoter. AAV vectors were titer matched at 5 × 10 11 genomic copies (GC)/ml and 1 μl was injected into the red nucleus. The proportion of transduced neurons in the red nucleus was determined at 1 and 4 weeks post-injection. AAV1 would be the vector of choice if the aim would be to overexpress a transgene at high level for a longer period of time. AAV5 and AAV8 would be the preferred serotype if onset of expression is should be somewhat delayed. The use of lentiviral vectors should be considered when transduction of both glial cells and neurons is required. Serotypes 3 and 4 did not transduce red nucleus neurons. AAV1, AAV6 and LV would be the vectors of choice if the aim of the experiment would be to rapidly express a transgene. The current data are important for the design of experiments that aim to study the effects of transgene products on the regenerative capacity of injured red nucleus neurons.

Effects of electro-acupuncture on signal transduction pathway of hypothalamic neuroendocrine system in ovariectomized rats

To compare the varieties and contents of the main nerval information molecules in perfusate from hypothalamic medial preoptic area (MPOA) of the rats in different sexual cycles and the ovariectomized rats treated by electro-acupuncture, so as to observe the similarities and differences of hypothalamic neuroendocrine signal transduction pathway under the physiological and pathological status, and to explore the mechanisms of neuroendocrine signal transduction of electro-acupuncture therapeutic effect in perimenopausal syndrome. The stereo localization technique and push-and-pull perfusion of the rat brain nucleus were adopted for collecting the hypothalamic MPOA perfusate of the female rats with normal sexual cycle, and also for collecting the MPOA perfusate of ovariectomized rats after electro-acupuncture treatment as acupuncture perfusate (AP). After being respectively microinjected into MPOA of the ovariectomized rats, the influence of the different perfusates on vagina cytology and serum estradiol (E2) level was observed. The contents of gonadotropin-releasing hormone (GnRH), dopamine (DA), gamma-aminobutyric acid (GABA), glutamate (Glu), aspartate (Asp) and beta-endorphin (beta-EP) in the perfusate of each group were detected by radioimmunoassay or high performance liquid chromatography, and then the varieties and contents of these substances in the perfusate of each group were compared and analyzed. The contents of neural active substances including DA, GABA, Glu, and beta-EP in the perfusate from the rats' MPOA during different stages of sexual cycle showed some regular changes. After the perfusate was microinjected respectively into the MPOA of the ovariectomized rats, the changes of animal vaginal exfoliated cells and serum E2 level showed the similar four-stage cycle characteristics as normal rats; the changes of vaginal exfoliated cells and serum E2 level of the ovariectomized rats without electro-acupuncture treatment showed the acupuncture-like effects following the microinjection of AP in the MPOA. The information molecules in the perfusate from MPOA of rats in normal sexual cycle or electro-acupuncture-treated rats include classical neurotransmitters, amino acid neurotransmitters, and neuropeptides. Acupuncture may modulate the release and synthesis of these information molecules to normalize the subnormal function of MPOA in perimenopausal period. Thus, AP may be a neuroendocrine signal carrier of acupuncture effects for acupuncture signal transduction from one individual to another. This may provide a new thinking and method for studying acupuncture signal transduction of the acupuncture therapeutic effects on perimenopausal syndrome.

W2029 Restraint and Abdominal Surgery Activate Nesfatin-1 Immunoreactive Brain Nuclei in Rats

W2029 Restraint and Abdominal Surgery Activate Nesfatin-1 Immunoreactive Brain Nuclei in Rats<B/>

937. Adeno-Associated Viral Vector (AAV)-Mediated Gene Transfer in the Red Nucleus of the Adult Rat Brain: Comparative Analysis of the Transduction Properties of Seven AAV Serotypes and Lentiviral Vectors

937. Adeno-Associated Viral Vector (AAV)-Mediated Gene Transfer in the Red Nucleus of the Adult Rat Brain: Comparative Analysis of the Transduction Properties of Seven AAV Serotypes and Lentiviral Vectors

Nesfatin-1 immunoreactivity in rat brain and spinal cord autonomic nuclei

Nesfatin-1 is one of the peptide products of posttranslational processing of the nucleobindin-2 (NUCB2) gene, suggested to have physiological relevance to suppress food intake and body weight gain in rats. Nesfatin-1-immunoreactive cells have been found in distinct nuclei in the rat brain related to circuitries regulating food intake. Here, we report novel yet undescribed localization of NUCB2/nesfatin-1 at the mRNA and protein level in the rat central nervous system. Immunohistochemical staining revealed the localization of NUCB2/nesfatin-1 in the piriform and insular cortex, endopiriform nucleus, nucleus accumbens, lateral septum, bed nucleus of stria terminalis, central amygdaloid nucleus, medial preoptic area, dorsal raphe nucleus, ambiguus nucleus, ventrolateral medulla and gigantocellular reticular nucleus, as well as Purkinje-cells of the cerebellum. In the spinal cord, nesfatin-1 immunoreactivity (IR) was found in both sympathetic and parasympathetic preganglionic neuronal groups and in the dorsal area X from lower thoracic to sacral segments. The immunohistochemical results were confirmed by RT-PCR in the central amygdaloid nucleus, nucleus accumbens, cerebellum and lumbar spinal cord microdissected by punch technique. The features and distributions of nesfatin-1 IR and mRNA expression in the brain and spinal cord suggest that NUCB2/nesfatin-1 could play a wider role in autonomic regulation of visceral-endocrine functions besides food intake.

Effects of ginseng saponin on acute cocaine-induced alterations in evoked dopamine release and uptake in rat brain nucleus accumbens

In traditional medicine, Panax ginseng has been used to treat various behavioral effects of psychostimulants (e.g., cocaine) and other drugs of abuse and to ameliorate withdrawal symptoms. The neurochemical bases for this efficacy, however, remain to be elucidated. We previously used the real-time fast-scan cyclic voltammetry in rat nucleus accumbens slices to demonstrate that cocaine not only enhances DA release evoked by single-pulse electrical stimulation and inhibits DA uptake during application but also further increases the release upon washout (termed a “rebound” release enhancement). In the present study, we determined whether co-application and washout of ginseng total saponin (GTS), the active ingredient of Panax ginseng, with cocaine attenuate cocaine-induced enhancement of evoked DA release, DA uptake inhibition and/or withdrawal-associated rebound enhancement. Cocaine rapidly potentiated the DA release within the first 10 min of application, and acute cocaine withdrawal caused a rebound increase. Co-application of GTS with cocaine inhibited the release enhancement and subsequently prevented the rebound increase during acute withdrawal. The effect of GTS was concentration-dependent. In contrast, GTS had no significant effects on the cocaine-mediated DA uptake inhibition. These results suggest that the attenuation of the cocaine-induced enhancement of impulse-dependent DA release, rather than uptake inhibition, might be one of the pharmacological bases for attenuation of behavioral effects of cocaine and amelioration of acute withdrawal symptoms by ginseng.

Nonclassical Mechanisms of Progesterone Action in the Brain: II. Role of Calmodulin-Dependent Protein Kinase II in Progesterone-Mediated Signaling in the Hypothalamus of Female Rats

In addition to the activation of classical progestin receptor-dependent genomic pathway, progesterone (P) can activate nonclassical, membrane-initiated signaling pathways in the brain. We recently demonstrated rapid P activation of second-messenger kinases, protein kinase A, and protein kinase C in the ventromedial nucleus (VMN) and preoptic area (POA) of rat brain. To determine whether P can activate yet another Ca+2 dependent kinase, we examined the rapid P modulation of calcium and calmodulin-dependent protein kinase II (CaMKII) in the VMN and POA in female rats. A rapid P-initiated activation of CaMKII basal activity was observed in the VMN but not the POA at 30 min. Estradiol benzoate (EB) priming enhanced this CaMKII basal activity in both the VMN and POA. CaMKII protein levels and phosphorylation of Thr-286 moiety on CaMKII, however, remained unchanged with EB and/or P treatments, suggesting that the changes in the CaMKII kinase activity are due to rapid P modulation of the kinase activity and not its synthesis or autoactivation. Furthermore, intracerebroventricular (icv) administration of a CaMKII-specific inhibitor, KN-93, 30 min prior to the P infusion, in EB-primed, ovariectomized female rats inhibited CaMKII activation but not protein kinase A and protein kinase C activities. Interestingly, icv administration of KN-93 30 min prior to P infusion (icv) resulted in a reduction but not total inhibition of P-facilitated lordosis response in EB-primed female rats. These observations suggest a redundancy or, alternately, a hierarchy in the P-regulated activation of kinase signaling cascades in female reproductive behavior.

Expression Of Epithelial Na+ Channel (ENaC) And Serum/glucocorticoid Regulated Kinase 1 (SGK1) In Brain Nuclei of Rats Post‐MI

Blockade of brain mineralocorticoid receptors (MR) or ENaC prevents sympathetic hyperactivity and improves cardiac function in rats post MI. To assess whether this response reflects increases in ENaC activity, we studied mRNA expression of ENaC (α, β, γ) subunits and SGK1, an important regulator of ENaC, in brain nuclei of male Wistar rats at 2 &amp; 4 weeks (wks) post MI. Micro‐punches were taken from the subfornical organ (SFO), paraventricular nucleus (PVN) and supraoptic nucleus (SON). Expression of mRNA was measured by real‐time qRT‐PCR, normalized by house keeping gene phosphoglycerate kinase 1 (PGK1). In SFO, α and β subunit mRNA levels significantly increased at 4 (1.7±0.2 vs 1.2±0.1 α/PGK1 [×10−3]; 1.0±0.1 vs 0.6±0.1 β/PGK1 [×10−4]) but not 2 wks compared to sham. In PVN, α subunit mRNA levels decreased at 2 (2.9±0.5 vs 4.5±0.6 [×10−3], p&lt;0.05) but not 4 wks post MI. In contrast, mRNA levels of γ subunit significantly increased at 4 (1.2±0.2 vs 0.6±0.2 [×10−4]) but not 2 wks. No changes of ENaC subunit mRNA was found in SON. mRNA levels of SGK1 were similar in SFO, PVN and SON between MI and sham at 2 &amp; 4 wks. These results indicate that in rats post MI, ENaC subunit mRNA expression is differentially regulated in brain nuclei. SGK1 transcription regulation appears not to be involved. Upregulation of ENaC subunit transcription in SFO and PVN may increase ENaC activity and thereby contribute to sympathetic hyperactivity.

Regulation of Progesterone Receptor Expression by Estradiol Is Dependent on Age, Sex and Region in the Rat Brain

Progesterone receptor (PR) expression is highly dependent on estradiol in the medial preoptic nucleus (MPN) and the ventromedial nucleus (VMN) of the adult rat brain. During development, males express high levels of PR in the MPN, whereas females have virtually no PR, a sex difference resulting entirely from differential exposure to estradiol. Because PR is also estradiol dependent in the adult VMN, the present study examined the regulation of PR immunoreactivity (PRir) in the developing VMN. Surprisingly, PRir was present at high levels in the VMN of both neonatal males and females. In the neonatal VMN, PR expression was dependent on gonadal hormones in males but not females. When females were ovariectomized and exposed to estradiol at various ages from neonatal to adulthood, estradiol reliably induced PRir in the MPN at postnatal d 7 but failed to induce PRir in the VMN of the same animals. Only later in development, around postnatal d 14, did estradiol increase PRir in the female VMN. There appears to be a developmental switch in the VMN when PR expression changes from estradiol independent to estradiol dependent. Furthermore, this switch is anatomically specific and does not exist in the MPN. The present results indicate that the regulation of PR expression by estradiol is dependent on age, sex, and brain region, suggesting that PR may play a critical but specific role in the normal development of these reproductively important brain areas. In addition, the neonatal female VMN may provide a unique model in which to examine the mechanisms underlying the specificity of steroid-induced gene expression.

Serum amyloid P component induces TUNEL-positive nuclei in rat brain after intrahippocampal administration

Serum amyloid P component (SAP)-induced neuronal apoptosis has been demonstrated on the primary culture of embryonic rat cerebral cortex in vitro. Here we present pieces of evidence that cell death is also induced by serum amyloid P component in living rat brain similarly to that in cell culture. Intrahippocampally administered SAP diffuses from the site of injection to the cortical and subcortical area of the rat brain and enters the cells of brain tissue in 1 week. It induces elevation of the number of in situ TdT-mediated dUTP-X nick end-labeled nuclei in the hippocampus, cortex and subcortical structures of rat central nervous system. DNA fragmentation, which is detected by the end labeling reaction, is characteristic to apoptosis. It develops in 4 weeks following exposure. Apoptosis is an important form of cell death in different neurodegenerative diseases including Alzheimer's disease. Our present work reveals that apoptosis can be induced by SAP beyond other hitherto known apoptosis inducing components of neurodegeneration. Hereby SAP seems to be an important component of the process, which leads to expanded neuronal loss in the pathomechanism of neurodegenerative diseases.

AVPV neurons containing estrogen receptor-beta in adult male rats are influenced by soy isoflavones

BackgroundIsoflavones, the most abundant phytoestrogens in soy foods, are structurally similar to 17beta-estradiol. It is known that 17beta-estradiol induces apoptosis in anteroventral periventricular nucleus (AVPV) in rat brain. Also, there is evidence that consumption of soy isoflavones reduces the volume of AVPV in male rats. Therefore, in this study, we examined the influence of dietary soy isoflavones on apoptosis in AVPV of 150 day-old male rats fed either a soy isoflavone-free diet (Phyto-free) or a soy isoflavone-rich diet (Phyto-600).ResultsThe occurrence of apoptosis in AVPV was examined by TUNEL staining. The incidence of apoptosis was about 10 times higher in the Phyto-600 group (33.1 ± 1.7%) than in the Phyto-free group (3.6 ± 1.0%). Furthermore, these apoptotic cells were identified as neurons by dual immunofluorescent staining of GFAP and NeuN as markers of astrocytes and neurons, respectively. Then the dopaminergic neurons in AVPV were detected by immunohistochemistry staining of tyrosine hydroxylase (TH). No significant difference in the number of TH neurons was observed between the diet treatment groups. When estrogen receptor (ER) alpha and beta were examined by immunohistochemistry, we observed a 22% reduction of ERbeta-positive cell numbers in AVPV with consumption of soy isoflavones, whereas no significant change in ERalpha-positive cell numbers was detected. Furthermore, almost all the apoptotic cells were ERbeta-immunoreactive (ir), but not ERalpha-ir. Last, subcutaneous injections of equol (a major isoflavone metabolite) that accounts for approximately 70–90% of the total circulating plasma isoflavone levels did not alter the volume of AVPV in adult male rats.ConclusionIn summary, these findings provide direct evidence that consumption of soy isoflavones, but not the exposure to equol, influences the loss of ERbeta-containing neurons in male AVPV.

Expression of Mineralocorticoid Receptors (MR) and Epithelial Na+ Channel (ENaC) Subunits in the Heart and Brain Nuclei of Rats Post‐MI

Blockade of central and peripheral MR in rats post MI attenuates sympathetic hyperactivity and ameliorates LV remodeling. The mechanisms involved are not yet clear. We studied mRNA expression of MR and ENaC (α, β, γ) subunits by real-time qRT-PCR and aldosterone binding densities by autoradiography in heart and brain nuclei of male Wistar rats at 2 & 4 wks post MI. Binding densities increased in LV and 2 brain nuclei, but decreased markedly in the infarct scar (table). MR mRNA decreased only at 2 wks; in SFO and OVLT (5.6±0.7 vs. 7.9±0.5, p<0.05; 2.9±0.4 vs. 5.4±0.6, p=0.05; MR/PGK [×10−2]) and showed no changes in LV and other nuclei. ENaC mRNA levels significantly increased in the scar vs. non-infarct LV & sham (41.0±6.0 vs. 3.8±1.0 & 1.5±0.4, for α; 11.3±1.0 vs. 0.3±0.1& non detectable levels for β, and 25.6±5.0 vs. 0.2±0.04 & 0.3±0.1for γ; ENaC/PGK [×10−4]). These results indicate that in rats post MI, MR expression is differentially regulated in brain nuclei. Upregulation of aldosterone binding densities and ENaC transcription in heart and brain may contribute to LV remodeling.

Differential regulation of the neuronal isoform of nitric oxide synthase in the superior colliculus and dorsal lateral geniculate nucleus of the adult rat brain following eye enucleation

Nitric oxide has been shown to play various physiological and pathological roles in the visual system. We studied here the expression of the neuronal isoform of nitric oxide synthase in the rat superior colliculus and in the dorsal lateral geniculate nucleus after unilateral enucleation, by means of immunohistochemistry, immunoblotting, and real-time PCR. Immunohistochemistry revealed an increase of nitric oxide synthase-positive neurons in specific layers of the superior colliculus and in the dorsal lateral geniculate nucleus between 1 and 30 days post-lesion. Immunoblotting analyses confirmed that the neuronal isoform of nitric oxide synthase is upregulated in the superior colliculus and in the dorsal lateral geniculate nucleus after retinal removal. Diaminofluorescein histochemistry suggested that nitric oxide production was increased in both deafferented retinorecipient areas. Our real-time PCR results indicated that nitric oxide synthase transcript levels in the superior colliculus were not significantly altered after monocular enucleation, although an upregulation of the enzyme transcription was detected into the deafferented dorsal lateral geniculate nucleus. These findings indicated that neuronal nitric oxide synthase may undergo different forms of regulation in the adult deafferented visual system.

TTF-1, a homeodomain-containing transcription factor, regulates feeding behavior in the rat hypothalamus

TTF-1 is a member of the NKx family of homeodomain genes, and is required for morphogenesis and fetal diencephalon development. Our previous studies have shown that TTF-1 expression is maintained in some regions of the postnatal rat brain and transactivates the gene expression of several neuropeptides. In this study, a potential role for TTF-1 in the regulation of feeding behavior was identified. Immunohistochemical analysis showed that TTF-1 is present in several hypothalamic nuclei of the adult rat brain involved in the control of feeding behavior. Food deprivation for two days markedly increased the hypothalamic levels of TTF-1 mRNA and protein. Intracerebroventricular administration of an antisense TTF-1 oligodeoxynucleotide significantly decreased TTF-1 protein abundance in the hypothalamus. This TTF-1 decrease was followed by a significant decrease in neuropeptide Y mRNA content and an increase in proopiomelanocortin mRNA content, and in turn resulted in a decrease of the animal’s food intake and body weight. These results suggest a novel role for TTF-1 in the regulation of feeding behavior in the rat hypothalamus.