title: Toll-like receptor 9 deficiency impacts sensory and motor behaviors.
abstract: Toll-like receptors (TLRs) mediate the induction of the innate immune system in response to pathogens, injury and disease. However, they also play non-immune roles and are expressed in the central nervous system (CNS) during prenatal and postnatal stages including adulthood. Little is known about their roles in the CNS in the absence of pathology. Several members of the TLR family have been implicated in the development of neural and cognitive function although the contribution of TLR9 to these processes has not been well defined. The current studies were undertaken to determine whether developmental TLR9 deficiency affects motor, sensory or cognitive functions. We report that TLR9 deficient (TLR9(-/-)) mice show a hyper-responsive sensory and motor phenotype compared to wild type (TLR9(+/+)) controls. This is indicated by hypersensitivity to thermal stimuli in the hot plate paw withdrawal test, enhanced motor-responsivity under anxious conditions in the open field test and greater sensorimotor reactivity in the acoustic startle response. Prepulse inhibition (PPI) of the acoustic startle response was also enhanced, which indicates abnormal sensorimotor gating. In addition, subtle, but significant, gait abnormalities were noted in the TLR9(-/-) mice on the horizontal balance beam test with higher foot slip numbers than TLR9(+/+) controls. In contrast, spatial learning and memory, assessed by the Morris water maze, was similar in the TLR9(-/-) and TLR9(+/+) mice. These findings support the notion that TLR9 is important for the appropriate development of sensory and motor behaviors.
authors.affiliation: Department of Neurological Surgery, The Spine Center of New Jersey, Reynolds Family Spine Laboratory, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA. Kharivve@umdnj.edu
authors.forename: Veronika
authors.initials: V
authors.lastname: Khariv
authors.forename: Kevin
authors.initials: K
authors.lastname: Pang
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Servatius
authors.forename: Brian T
authors.initials: BT
authors.lastname: David
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Goodus
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Beck
authors.forename: Robert F
authors.initials: RF
authors.lastname: Heary
authors.forename: Stella
authors.initials: S
authors.lastname: Elkabes
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000523:psychology; D001522:Behavior, Animal / Q000502:physiology*; D005260:Female; D006185:Habituation, Psychophysiologic / Q000235:genetics / Q000502:physiology; D018737:Hand Strength / Q000502:physiology; D006624:Hippocampus / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics* / Q000502:physiology*; D009069:Movement Disorders / Q000235:genetics / Q000523:psychology; D010146:Pain / Q000235:genetics / Q000523:psychology; D010641:Phenotype; D004856:Postural Balance / Q000235:genetics / Q000502:physiology; D013216:Reflex, Startle / Q000235:genetics / Q000502:physiology; D012677:Sensation / Q000235:genetics* / Q000502:physiology*; D051217:Toll-Like Receptor 9 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*
chemical_list: D051217:Toll-Like Receptor 9