Skip to main content
SpringerLink
Log in

Immunohistochemical Distribution of Somatostatin and Somatostatin Receptor Subtypes (SSTR1–5) in Hypothalamus of ApoD Knockout Mice Brain

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

In the present study, the expression of somatostatin (SST) and somatostatin receptor subtypes (SSTR1–5) was determined in the hypothalamus of wild-type (wt) and apolipoprotein D knockout (ApoD−/−) mice brain. SST-like immunoreactivity, while comparable in most regions of hypothalamus, diminished significantly in arcuate nucleus of ApoD−/− mice. SSTR1 strongly localized in all major hypothalamic nuclei as well as in the median eminence and ependyma of the third ventricle of wt mice brain. SSTR1-like immunoreactivity increases in hypothalamus except in paraventricular nucleus of ApoD−/− mice. SSTR2 was well expressed in most of the hypothalamic regions whereas it decreases significantly in ventromedial and arcuate nucleus of ApoD−/− mice. SSTR3 and SSTR4-like immunoreactivity increases in ApoD−/− mice in all major nuclei of hypothalamus, median eminence, and ependymal cells of third ventricle. SSTR5 is well expressed in ventromedial and arcuate nucleus whereas weakly expressed in paraventricular nucleus. In comparison to wt, ApoD−/− mice exhibit increased SSTR5-like immunoreactivity in paraventricular nuclei and decreased receptor expression in ventromedial hypothalamus and arcuate nucleus. In conclusion, the changes in hypothalamus of ApoD−/− mice may indicate potential role of ApoD in regulation of endocrine functions of somatostatin in a receptor-dependent manner.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Abbreviations

ApoD:

Apolipoprotein D

AN:

Arcuate nucleus

DMH:

Dorsomedial hypothalamic nucleus

GH:

Growth hormone

GPCR:

G-protein coupled receptor

HPA:

Hypothalamo-pituitary-adrenal axis

ME:

Median eminence

PVN:

Paraventricular nucleus

PeVN:

Periventricular nucleus

PRL:

Prolactin

VMH:

Ventromedial hypothalamic nucleus

SST:

Somatostatin

SSTR:

Somatostatin receptor

3V:

Third ventricle

wt :

Wild type

References

  • Baragli A, Alturaihi H, Watt HL, Abdallah A, Kumar U (2007) Heterooligomerization of human dopamine receptor 2 and somatostatin receptor 2 co-immunoprecipitation and fluorescence resonance energy transfer analysis. Cell Signal 19:2304–2316

    Article  PubMed  CAS  Google Scholar 

  • Ben-Shlomo A, Melmed S (2008) Somatostatin agonists for treatment of acromegaly. Mol Cell Endocrinol 286:192–198

    Article  PubMed  CAS  Google Scholar 

  • Boer S, Sanchez D, Reinieren I et al (2010) Decreased kainate receptors in the hippocampus of apolipoprotein D knockout mice. Prog Neuropsychopharmacol Biol Psychiatry 34:271–278

    Article  PubMed  CAS  Google Scholar 

  • Colao A, Faggiano A, Pivonello R (2010) Somatostatin analogues: treatment of pituitary and neuroendocrine tumors. Prog Brain Res 182:281–294

    Article  PubMed  CAS  Google Scholar 

  • Dandoy-Dron F, Guillo F, Benboudjema L et al (1998) Gene expression in scrapie. Cloning of a new scrapie-responsive gene and the identification of increased levels of seven other mRNA transcripts. J Biol Chem 273:7691–7697

    Article  PubMed  CAS  Google Scholar 

  • Do Carmo S, Fournier D, Mounier C, Rassart E (2009) Human apolipoprotein D overexpression in transgenic mice induces insulin resistance and alters lipid metabolism. Am J Physiol Endocrinol Metab 296:E802–E811

    Article  PubMed  Google Scholar 

  • Ganfornina MD, Do CS, Lora JM et al (2008) Apolipoprotein D is involved in the mechanisms regulating protection from oxidative stress. Aging Cell 7:506–515

    Article  PubMed  CAS  Google Scholar 

  • Goodyer CG, Grigorakis SI, Patel YC, Kumar U (2004) Developmental changes in the expression of somatostatin receptors (1–5) in the brain, hypothalamus, pituitary and spinal cord of the human fetus. Neuroscience 125:441–448

    Article  PubMed  CAS  Google Scholar 

  • Grant M, Collier B, Kumar U (2004a) Agonist-dependent dissociation of human somatostatin receptor 2 dimers: a role in receptor trafficking. J Biol Chem 279:36179–36183

    Article  PubMed  CAS  Google Scholar 

  • Grant M, Patel RC, Kumar U (2004b) The role of subtype-specific ligand binding and the C-tail domain in dimer formation of human somatostatin receptors. J Biol Chem 279:38636–38643

    Article  PubMed  CAS  Google Scholar 

  • Hildebrand MS, de Silva MG, Klockars T et al (2005) Expression of the carrier protein apolipoprotein D in the mouse inner ear. Hear Res 200:102–114

    Article  PubMed  CAS  Google Scholar 

  • Kalman J, McConathy W, Araoz C, Kasa P, Lacko AG (2000) Apolipoprotein D in the aging brain and in Alzheimer’s dementia. Neurol Res 22:330–336

    PubMed  CAS  Google Scholar 

  • Khan MM, Evans DR, Gunna V et al (2002) Reduced erythrocyte membrane essential fatty acids and increased lipid peroxides in schizophrenia at the never-medicated first-episode of psychosis and after years of treatment with antipsychotics. Schizophr Res 58:1–10

    Article  PubMed  Google Scholar 

  • Kim WS, Wong J, Weickert CS et al (2009) Apolipoprotein-D expression is increased during development and maturation of the human prefrontal cortex. J Neurochem 109:1053–1066

    Article  PubMed  CAS  Google Scholar 

  • Kumar U (2005) Expression of somatostatin receptor subtypes (SSTR1–5) in Alzheimer’s disease brain: an immunohistochemical analysis. Neuroscience 134:525–538

    Article  PubMed  CAS  Google Scholar 

  • Kumar U (2007) Colocalization of somatostatin receptor subtypes (SSTR1–5) with somatostatin, NADPH-diaphorase (NADPH-d), and tyrosine hydroxylase in the rat hypothalamus. J Comp Neurol 504:185–205

    Article  PubMed  CAS  Google Scholar 

  • Kumar U, Grant M (2010) Somatostatin and somatostatin receptors. Results Probl Cell Differ 50:137–184

    PubMed  CAS  Google Scholar 

  • Kumar U, Laird D, Srikant CB, Escher E, Patel YC (1997) Expression of the five somatostatin receptor (SSTR1–5) subtypes in rat pituitary somatotrophs: quantitative analysis by double-layer immunofluorescence confocal microscopy. Endocrinology 138:4473–4476

    Article  PubMed  CAS  Google Scholar 

  • Kumar U, Sasi R, Suresh S et al (1999) Subtype-selective expression of the five somatostatin receptors (hSSTR1–5) in human pancreatic islet cells: a quantitative double-label immunohistochemical analysis. Diabetes 48:77–85

    Article  PubMed  CAS  Google Scholar 

  • Liu Z, Chang GQ, Leibowitz SF (2001) Apolipoprotein D interacts with the long-form leptin receptor: a hypothalamic function in the control of energy homeostasis. FASEB J 15:1329–1331

    Article  PubMed  CAS  Google Scholar 

  • Low MJ, Otero-Corchon V, Parlow AF et al (2001) Somatostatin is required for masculinization of growth hormone-regulated hepatic gene expression but not of somatic growth. J Clin Invest 107:1571–1580

    Article  PubMed  CAS  Google Scholar 

  • Navarro A, Tolivia J, Astudillo A, del Valle E (1998) Pattern of apolipoprotein D immunoreactivity in human brain. Neurosci Lett 254:17–20

    Article  PubMed  CAS  Google Scholar 

  • Navarro A, Alonso A, Garrido P et al (2010) Increase in placental apolipoprotein D as an adaptation to human gestational diabetes. Placenta 31:25–31

    Article  PubMed  CAS  Google Scholar 

  • Ong WY, He Y, Suresh S, Patel SC (1997) Differential expression of apolipoprotein D and apolipoprotein E in the kainic acid-lesioned rat hippocampus. Neuroscience 79:359–367

    Article  PubMed  CAS  Google Scholar 

  • Ordonez C, Navarro A, Perez C et al (2006) Apolipoprotein D expression in substantia nigra of Parkinson disease. Histol Histopathol 21:361–366

    PubMed  CAS  Google Scholar 

  • Patel YC (1999) Somatostatin and its receptor family. Front Neuroendocrinol 20:157–198

    Article  PubMed  CAS  Google Scholar 

  • Patel SC, Asotra K, Patel YC et al (1995) Astrocytes synthesize and secrete the lipophilic ligand carrier apolipoprotein D. Neuroreport 6:653–657

    Article  PubMed  CAS  Google Scholar 

  • Patel SC, Alturaihi H, Baragli A, Smith JD, Ong W, Kumar U (2003) Dopamine receptor expression in ApoD−/−, NPC−/− and ApoD−/−NPC−/− mice. Society for Neuroscience meeting, November 8–13; New Orleans, LA

  • Perdomo G, Kim DH, Zhang T et al (2010) A role of apolipoprotein D in triglyceride metabolism. J Lipid Res 51:1298–1311

    Article  PubMed  CAS  Google Scholar 

  • Rajput PS, Billova S, Patel SC et al (2009) Expression of somatostatin and somatostatin receptor subtypes in apolipoprotein D (ApoD) knockout mouse brain: an immunohistochemical analysis. J Chem Neuroanat 38:20–33

    Article  PubMed  CAS  Google Scholar 

  • Ramirez JL, Mouchantaf R, Kumar U et al (2002) Brain somatostatin receptors are up-regulated in somatostatin-deficient mice. Mol Endocrinol 16:1951–1963

    Article  PubMed  CAS  Google Scholar 

  • Ramirez JL, Grant M, Norman M et al (2004) Deficiency of somatostatin (SST) receptor type 5 (SSTR5) is associated with sexually dimorphic changes in the expression of SST and SST receptors in brain and pancreas. Mol Cell Endocrinol 221:105–119

    Article  PubMed  CAS  Google Scholar 

  • Rassart E, Bedirian A, Do CS et al (2000) Apolipoprotein D. Biochim Biophys Acta 1482:185–198

    Article  PubMed  CAS  Google Scholar 

  • Rickhag M, Wieloch T, Gido G et al (2006) Comprehensive regional and temporal gene expression profiling of the rat brain during the first 24 h after experimental stroke identifies dynamic ischemia-induced gene expression patterns, and reveals a biphasic activation of genes in surviving tissue. J Neurochem 96:14–29

    Article  PubMed  CAS  Google Scholar 

  • Rocheville M, Lange DC, Kumar U et al (2000) Receptors for dopamine and somatostatin: formation of hetero-oligomers with enhanced functional activity. Science 288:154–157

    Article  PubMed  CAS  Google Scholar 

  • Somvanshi RK, Billova S, Kharmate G, Rajput PS, Kumar U (2009) C-tail mediated modulation of somatostatin receptor type-4 homo- and heterodimerizations and signaling. Cell Signal 21:1396–1414

    Article  PubMed  CAS  Google Scholar 

  • Strowski MZ, Blake AD (2008) Function and expression of somatostatin receptors of the endocrine pancreas. Mol Cell Endocrinol 286:169–179

    Article  PubMed  CAS  Google Scholar 

  • Suresh S, Yan Z, Patel RC, Patel YC, Patel SC (1998) Cellular cholesterol storage in the Niemann–Pick disease type C mouse is associated with increased expression and defective processing of apolipoprotein D. J Neurochem 70:242–251

    Article  PubMed  CAS  Google Scholar 

  • Terrisse L, Poirier J, Bertrand P et al (1998) Increased levels of apolipoprotein D in cerebrospinal fluid and hippocampus of Alzheimer’s patients. J Neurochem 71:1643–1650

    Article  PubMed  CAS  Google Scholar 

  • Thomas EA, Dean B, Pavey G, Sutcliffe JG (2001) Increased CNS levels of apolipoprotein D in schizophrenic and bipolar subjects: implications for the pathophysiology of psychiatric disorders. Proc Natl Acad Sci U S A 98:4066–4071

    Article  PubMed  CAS  Google Scholar 

  • Thomas EA, George RC, Sutcliffe JG (2003) Apolipoprotein D modulates arachidonic acid signaling in cultured cells: implications for psychiatric disorders. Prostaglandins Leukot Essent Fat Acids 69:421–427

    Article  CAS  Google Scholar 

  • War SA, Foot EA, Somvanshi RK et al (2010) Expression of somatostatin receptors in the diabetic brain of db/db mouse model. Endocr Rev S1:S182

    Google Scholar 

Download references

Acknowledgments

This work was supported by the Canadian Institute of Health Research Grant (MOP 10268 and MOP 74465) to UK. Author is thankful to Dr. Shutish C. Patel for providing ApoD−/− mice and all personnel from the laboratory for the help in preparation of this manuscript. UK is a senior Scholar of Michael Smith Foundation for Health and Research.

Competing Interest

The author declares no competing interests.

Author information

Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, V6T 1Z3, Canada

    Ujendra Kumar

Authors
  1. Ujendra Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ujendra Kumar.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kumar, U. Immunohistochemical Distribution of Somatostatin and Somatostatin Receptor Subtypes (SSTR1–5) in Hypothalamus of ApoD Knockout Mice Brain. J Mol Neurosci 48, 684–695 (2012). https://doi.org/10.1007/s12031-012-9792-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-012-9792-7

Keywords

Search

Navigation