The lateral parabrachial nucleus is a site of action for neuroendocrine signaling effects on food intake / Alhadeff, Amber L.

Format:

Book

Thesis/Dissertation

Author/Creator:

Alhadeff, Amber L., author.

Contributor:

Hayes, Matthew R., degree supervisor.

Grill, Harvey J., 1948- degree supervisor.

Lucki, Irwin, degree committee member.

Flanagan-Cato, Loretta M., degree committee member.

University of Pennsylvania. Psychology, degree granting institution.

Language:

English

Subjects (All):

Physiological psychology.

Neurosciences.

Behavioral psychology.

Psychology--Penn dissertations.

Penn dissertations--Psychology.

Local Subjects:

Physiological psychology.

Neurosciences.

Behavioral psychology.

Psychology--Penn dissertations.

Penn dissertations--Psychology.

Genre:

Academic theses.

Physical Description:

1 online resource (144 pages)

Contained In:

Dissertation Abstracts International 76-11B(E).

Place of Publication:

[Philadelphia, Pennsylvania]: University of Pennsylvania ; Ann Arbor : ProQuest Dissertations & Theses, 2015.

Language Note:

English

System Details:

Mode of access: World Wide Web.

text file

Summary:

The dramatic increase in obesity and its associated comorbidities is a major public health concern. Given that obesity can be caused by increased calorie intake, it is necessary to understand the neural control of food intake in order to develop more effective obesity treatments. However, our knowledge of the brain regions and signaling mechanisms that are involved in energy balance is incomplete. This dissertation focuses on a relatively understudied brain region, the lateral parabrachial nucleus (lPBN), and its contributions to food intake control. The presence of receptors in lPBN neurons for various key neuroendocrine signals, including glucagon-like peptide-1 (GLP-1), leptin, and peptide YY (PYY), led me to hypothesize that these peptides act within the lPBN to affect food intake. To test this hypothesis, I gave microinjections of these peptides, and/or receptor agonists and antagonists, directly into the lPBN and measured a variety of food intake-relevant measures in rats. First, I showed that lPBN GLP-1R stimulation reduces chow and high-fat diet intake, likely through direct projections from GLP-1-producing neurons in the nucleus tractus solitarius (NTS). Conversely, lPBN GLP-1R blockade increased chow and high-fat diet intake, demonstrating that endogenous lPBN GLP-1R signaling is physiologically relevant to the control of food intake. lPBN GLP-1R stimulation also decreased progressive ratio (PR) operant responding for palatable food, suggesting a role for lPBN GLP-1R signaling in food reward. Next, I showed that lPBN leptin injection significantly reduced chow and high-fat diet intake by reducing meal size, indicating possible interactions between lPBN leptin signaling and the processing of gastrointestinal satiation signaling. Leptin receptor signaling in the lPBN, however, had no effect on gastric emptying or on food reward parameters [i.e. PR responding and conditioned place preference for palatable food]. Finally, I demonstrated that both biologically active isoforms of PYY [(1-36) and (3-36)] increase food intake by potently increasing meal size, effects which may be mediated by neuronal projections from gigantocellular reticular nucleus PYY-producing neurons to the lPBN. Quantitative polymerase chain reaction data revealed that of the Y family of receptors that bind PYY, the Y1 receptor was most highly expressed in the lPBN. Behavioral results confirmed that pretreatment with a selective Y1 receptor antagonist abolished the intake-stimulatory effects of lPBN PYY (3-36), suggesting that the Y1 receptor mediates the hyperphagic effects of lPBN PYY. Taken together, these data are the first to show that multiple neuroendocrine peptides known to regulate food intake and energy balance, i.e. GLP-1, leptin, and PYY, can act in the lPBN to affect food intake. Overall, my results highlight the lPBN as a key nucleus in the distributed central nervous system control of food intake and energy balance.

Notes:

Source: Dissertation Abstracts International, Volume: 76-11(E), Section: B.

Advisors: Harvey J. Grill; Matthew R. Hayes; Committee members: Loretta M. Flanagan-Cato; Irwin Lucki.

Department: Psychology.

Ph.D. University of Pennsylvania 2015.

Local Notes:

School code: 0175

ISBN:

9781321850291

Access Restriction:

Restricted for use by site license.