{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T19:56:23Z","timestamp":1792871783209,"version":"4.5.0"},"reference-count":71,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Serotonin (5-hydroxytryptamine, 5-HT) is essential to mood regulation, and its dysfunction has been strongly connected to depression and anxiety disorders. The key enzyme for serotonin production is tryptophan hydroxylase 2 (TPH2); genetic abnormalities influencing TPH2 activity have been connected to mood disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Our study aims to understand the consequences of human TPH2 mutation\u2014TPH2 R439H in mice, especially depression and anxiety-like behaviors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Compared to wild-type, we employed 6-month-old knock-in mice, heterozygotes (one allele) and homozygotes (two alleles) expressing TPH2 R439H analogous to the human R441H TPH2 mutation. We examined behavioral differences between TPH2-KI and WT mice, heterozygotes and homozygotes, and males and females. Tail suspension and forced swim assessed depression-like behavior; open field and light-dark tests assessed anxiety and exploration; the Morris water maze tested memory and spatial learning; rotarod assessed balance and motor coordination; and the novel object test assessed recognition memory.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our findings demonstrate that TPH2 KI mice exhibited increased depression-like behavior in the forced swim and tail suspension tests; increased avoidance in the light-dark and open field tests revealed anxiety-like phenotypes. Furthermore, serotonin deficit decreased locomotion and coordination in the rotarod. In the novel object, recognition memory was impaired, but spatial learning and memory in the Morris water were unaffected. Homozygotes displayed more severe phenotypes than heterozygotes, indicating a gene dosage-dependent effect.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings extend prior behavioral characterizations of TPH2 KI mice by providing an integrated profile at 6-month age point, revealing domain-specific effects across mood, anxiety, locomotion, and recognition memory.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261442229","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T15:34:48Z","timestamp":1776267288000},"page":"1317-1334","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Behavioral consequences of serotonin deficiency in TPH2 knock-in mice: Implications for depression, anxiety, and cognitive dysfunction"],"prefix":"10.1177","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4393-7234","authenticated-orcid":false,"given":"Madhuri","family":"Bandaru","sequence":"first","affiliation":[{"name":"Texas Tech University Health Sciences Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvir","family":"Rainier","sequence":"additional","affiliation":[{"name":"Texas Tech University Health Sciences Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Ariful","family":"Islam","sequence":"additional","affiliation":[{"name":"Texas Tech University Health Sciences Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9560-9948","authenticated-orcid":false,"given":"P. Hemachandra","family":"Reddy","sequence":"additional","affiliation":[{"name":"Texas Tech University Health Sciences Center"},{"name":"Nutritional Sciences Department, College of Human Sciences, Texas Tech University, Lubbock, TX, USA"},{"name":"Texas Tech University Health Sciences Center"},{"name":"Texas Tech University Health Sciences Center"},{"name":"Texas Tech University Health Sciences Center"},{"name":"Texas Tech University Health Sciences Center"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22094837"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102414"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102459"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26031160"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27051680"},{"key":"e_1_3_3_7_2","first-page":"20221565","article-title":"All the brain's a stage for serotonin: the forgotten story of serotonin diffusion across cell membranes","volume":"289","author":"Andrews PW","year":"2022","unstructured":"Andrews PW, Bosyj C, Brenton L, et al. 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