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1.  Mutations in TMEM216 perturb ciliogenesis and cause Joubert, Meckel and related syndromes 
Nature genetics  2010;42(7):619-625.
Joubert syndrome (JBTS), related disorders (JSRD) and Meckel syndrome (MKS) are ciliopathies. We now report that MKS2 and JBTS2 loci are allelic and due to mutations in TMEM216, encoding an uncharacterized tetraspan transmembrane protein. JBTS2 patients displayed frequent nephronophthisis and polydactytly, and two cases conformed to the Oro-Facio-Digital type VI phenotype, whereas skeletal dysplasia was common in MKS fetuses. A single p.R73L mutation was identified in all patients of Ashkenazi Jewish descent (n=10). TMEM216 localized to the base of primary cilia, and loss of TMEM216 in patient fibroblasts or following siRNA knockdown caused defective ciliogenesis and centrosomal docking, with concomitant hyperactivation of RhoA and Dishevelled. TMEM216 complexed with Meckelin, encoded by a gene also mutated in JSRD and MKS. Abrogation of tmem216 expression in zebrafish led to gastrulation defects that overlap with other ciliary morphants. The data implicate a new family of proteins in the ciliopathies, and further support allelism between ciliopathy disorders.
PMCID: PMC2894012  PMID: 20512146
2.  The Effects of Aging on Memory for Sequentially Presented Objects in Rats 
Behavioral neuroscience  2009;123(6):1339-1345.
The current study investigated memory for sequentially presented objects in young rats 6 months of age (n=12) and aged rats 24 months of age (n=12). Rats were tested on a task involving three exploratory trials and one probe test. During the exploratory trials, the rat explored a set of three sequentially presented object pairs (A-A, B-B, and C-C) for 5 min per pair with a 3 min delay between each pair. Following the exploratory trials, a probe test was conducted where the rat was presented simultaneously with one object from the first exploratory trial (A) and one object from the third exploratory trial (C). Results from the three exploratory trials showed no significant age-related differences in exploration, indicating that 24 month old rats explored the object pairs as much as 6 month old rats. Results from the probe test demonstrated that 6 month old rats spent significantly more time exploring object A compared to object C, indicating that young rats show intact memory for the temporal order of the exploratory trial objects. In contrast, 24 month old rats showed no preference for object A and spent a relatively equal amount of time exploring objects A and C. The results suggest that temporal order memory may decline as a result of age-related changes in the rodent brain. In addition, the findings may reflect differences in attraction to objects with different memory strengths. Since no significant age-related differences were detected during the exploratory trials, age-related differences on the probe trial were not due solely to decreased exploration, motivation, or locomotion in aged rats.
PMCID: PMC2819214  PMID: 20001117
Aging; Temporal Order; Sequence; Fischer 344 Brown Norway; Object Memory
3.  Age-Related Changes in Associative Learning for Olfactory and Visual Stimuli in Rodents 
Memory for olfactory stimuli may be particularly affected by age-related brain changes in humans and may be an early indicator of cognitive impairment and Alzheimer's disease. Studies involving rats have offered insights into impaired cognition in aged animals, but few have examined odor memory. Therefore, it is unclear whether aged rats are a good model for possible age-related changes in odor memory in humans. Young (6 month old) and old (24 month old) rats were tested on associative learning tasks involving visual and olfactory stimuli. The first task examined age-related differences in discrimination and reversal learning for olfactory and visual stimuli; the second task utilized an associative contextual learning task involving olfactory and visual cues. Although old rats were able to perform the olfactory and visual discrimination tasks as well as young rats, old rats displayed significant age-related impairment on the reversal learning and contextual learning tasks. The results suggest that aging may have a similar deleterious effect on odor memory in rats and in humans. The findings may have important implications for the selection of memory paradigms for future research studies on aging. In addition, the use of an animal model to investigate the effects of aging on odor memory will allow researchers the ability to investigate how age-related neuroanatomical and neurochemical changes may result in impaired odor memory.
PMCID: PMC2849724  PMID: 19686218
Aging; Learning; Memory; Context; Olfactory; Visual Object
4.  Age-Related Changes in Conditioned Flavor Preference in Rats 
Behavioural brain research  2007;188(1):56-61.
Age-related changes have been documented in regions of the brain shown to process reward information. However, few studies have examined the effects of aging on associative memory for reward. The present study tested 7 mo old and 24 mo old rats on a conditioned flavor preference task. Half of the rats in each age group received an unsweetened grape-flavored solution (CS−) on odd-numbered days and a sweetened cherry-flavored solution (CS+) on even-numbered days. The remaining rats in each age group received a sweetened grape-flavored solution (CS+) on odd-numbered days and an unsweetened cherry-flavored solution (CS−) on even-numbered days. During the acquisition phase of testing, the designated solution (CS+ or CS−) was presented to each rat for 15 min daily across six consecutive days. On the preference phase, each rat received unsweetened cherry and unsweetened grape flavored solutions simultaneously for 15 min daily across four consecutive days. The 7 mo old rats showed a significant preference for the flavor that was previously sweetened during the acquisition phase (CS+) compared to the previously unsweetened solution (CS−) when the two unsweetened solutions were presented simultaneously during the preference phase of testing. In contrast, the 24 mo old rats did not show a preference and consumed roughly equal amounts of the previously sweetened (CS+) and unsweetened (CS−) solutions. Thus, the data suggest that the ability to form flavor-reward associations declines with increasing age, resulting in impaired conditioned flavor preference.
PMCID: PMC2274004  PMID: 18061286
Aging; Reward; Flavor; Associative Learning; Amygdala

Results 1-4 (4)