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At least 253 records · Page 14Linked to original sources
PubMed2006

Modulation of 5' splice site selection using tailed oligonucleotides carrying splicing signals.

BACKGROUND: We previously described the use of tailed oligonucleotides as a means of reprogramming alternative pre-mRNA splicing in vitro and in vivo. The tailed oligonucleotides that were used interfere with splicing because they contain a portion complementary to sequences immediately upstream of the target 5' splice site combined with a non-hybridizing 5' tail carrying binding sites for the hnRNP A1/A2 proteins. In the present study, we have tested the inhibitory activity of RNA oligonucleotides carrying different tail structures. RESULTS: We show that an oligonucleotide with a 5' tail containing the human beta-globin branch site sequence inhibits the use of the 5' splice site of Bcl-xL, albeit less efficiently than a tail containing binding sites for the hnRNP A1/A2 proteins. A branch site-containing tail positioned at the 3' end of the oligonucleotide also elicited splicing inhibition but not as efficiently as a 5' tail. The interfering activity of a 3' tail was improved by adding a 5' splice site sequence next to the branch site sequence. A 3' tail carrying a Y-shaped branch structure promoted similar splicing interference. The inclusion of branch site or 5' splice site sequences in the Y-shaped 3' tail further improved splicing inhibition. CONCLUSION: Our in vitro results indicate that a variety of tail architectures can be used to elicit splicing interference at low nanomolar concentrations, thereby broadening the scope and the potential impact of this antisense technology.

Alternative Splicing↗
PubMed2002

The integrin beta tail is required and sufficient to regulate adhesion signaling to Rac1.

Rac1 is a small Rho family GTPase that regulates changes in cell morphology associated with cell spreading and migration. Integrin-mediated adhesion is known to activate Rac1 and to regulate the interaction of Rac1 with downstream effectors. Currently, it is not clear how integrins signal Rac1 activation following cell adhesion. Integrin beta cytoplasmic domains (beta-tails) are known to be required for integrin-mediated cell spreading, and isolated beta tails expressed as tac-beta tail chimeras can inhibit cell spreading indicating that protein interactions with beta tails can regulate this process. Our recent studies demonstrated that the expression of constitutively activated Rac1 can restore cell spreading inhibited by tac beta tail chimeras, suggesting a role for Rac1 in the regulation of cell spreading by beta tails. Hence, we examined the role of beta tails in integrin activation of Rac1. By using recombinant wild-type and mutant integrin heterodimers, we demonstrate that integrin beta tails are required for adhesion to increase Rac1-GTP loading. We demonstrate that clustering tac-beta tail chimeras, on the surface of cells in suspension, activates Rac1. Thus, beta tails are not only required, but also sufficient for integrin-triggered Rac1 activation. Our findings indicate that integrin beta-tails are an important link between integrin engagement and Rac1 signaling, and that protein interactions initiated at beta tails are sufficient for integrins to regulate Rac1 activity.

Cell Adhesion↗
PubMed1996

Heterocercal tail function in leopard sharks: a three-dimensional kinematic analysis of two models

Two different models have been proposed to explain the function of the heterocercal tail in shark locomotion. The classical model proposes that, as a result of lift generated by the tail as it beats, the net force acting on the tail is directed dorsally and anteriorly. In contrast, Thomson's model suggests that the tail generates a net force directed through the shark's center of gravity, i.e. ventrally and anteriorly. In this study, we evaluate these two models by describing the three-dimensional kinematics of the heterocercal tail in the leopard shark Triakis semifasciata during swimming. Lateral and posterior views of the tail were examined from four individuals swimming in a flow tank at 1.2 L s-1 (where L is total length) using two high-speed video cameras filming simultaneously at 250 fields s-1. These two simultaneous views allowed eight landmarks on the tail to be followed in three dimensions through time. These landmarks allowed the tail to be divided into separate surfaces whose orientation over time was calculated. Points located anteriorly on the tail go through significantly smaller excursions and reach their maximum lateral excursion significantly earlier in the beat cycle than points on the trailing edge of the tail. Three-dimensional angle calculations show that the terminal lobe leads the ventral lobe through a beat, as predicted by the classical model. Dye-stream visualizations confirmed that this pattern of movement deflects water ventrally and posteriorly to the moving tail, providing strong support for the classical model. Additionally, our results show that a three-dimensional analysis is critical to understanding the function of the heterocercal tail.

Journal Article↗
PubMed1999

Inheritance of the "rat-tail" syndrome and its effect on calf performance.

A form of congenital hypotrichosis, commonly know as the "rat-tail syndrome," occurs in a small percentage of calves produced by crossing some Continental cattle breeds with cattle that are black in color. These calves are characterized by short, curly, malformed, sometimes sparse hair and a lack of normal tail switch development. In our first study, performance of 43 rat-tail calves was compared with that of 570 non-rat-tail calves of the same breeding and contemporary groups. All rat-tail calves were sired by Simmental bulls and were from cows with various percentages of Angus breeding. The rat-tail condition had no effect on birth weight, weaning weight, or gain from birth to weaning. However, rat-tail calves had significantly lower rates of gain during the winter months from weaning to yearling than non-rat-tail calves, resulting in a 19 kg lighter yearling weight. Gains of steers from yearling to slaughter were not significantly different, but rat-tail steers were 36 kg lighter (P = .01) and 13 d older (P = .15) at slaughter than the non-rat-tail steers. In a second study, Angus-Simmental F1 males and females with the rat-tail condition were mated to produce 64 F2 offspring that were used to determine the mode of inheritance of this syndrome. Analysis showed that the rat-tail syndrome is controlled by interacting genes at two loci. Cattle that express the syndrome must have at least one dominant gene for black color and be heterozygous at the other locus involved.

Animals↗
PubMed2002

[Cloning and sequencing of four microsatellite loci in Small Tail Han Sheep].

Small Tail Han sheep is an excellent local sheep breed in China. Small Tail Han sheep has significant characteristics of high prolificacy. The lambing percentage averaged 260 percent in Small Tail Han sheep. The genetic detection of 4 microsatellite loci OarAE101, OarHH35, BM143 and BMS2508 which were closely linked to the fecundity gene FecB in Booroola sheep was conducted in 159 sheep in Small Tail Han sheep, Dorset sheep, F1 hybzids(Dorset x Small Tail Han sheep). The results confirmed the genetic characteristics of codominance of microsatellite DNA. The PCR amplified products of microsatellites were detected by non-denatured (natural) polyacrylamide gel electrophoresis. The sequences of PCR amplification fragment of 6 clones of 4 microsatellite loci in Small Tail Han sheep were accepted by GenBank of National Center for Biotechnology Information, National Institutes of Health in USA, the GenBank accession numbers were AF394445, AF394446, AF394447, AF394448, AF394449, AF394450, respectively. The sequence homogeneity between OarAE101 in Small Tail Han sheep in this study and the ovine OarAE101 in GenBank was 98 percent. The sequence homogeneity between OarHH35 in Small Tail Han sheep in this study and the ovine OarHH35 in GenBank was 99 percent. The sequence homogeneity between BM143 in Small Tail Han sheep in this study and the bovine BM143 in GenBank was 95 percent. The sequence homogeneity between BMS2508 in Small Tail Han sheep in this study and the bovine BMS2508 in GenBank was 95 percent. OarAE101, OarHH35, BM143 and BMS2508 in Small Tail Han sheep were all perfect microsatellites. These results could provide molecular basic data for the research on the germplasm characteristics of Small Tail Han sheep.

Animals↗
PubMed1993

Role of calcium ion in Schistosoma mansoni cercarial tail loss induced by unsaturated fatty acids.

Linoleate (C18: 2) and oleate (C18: 1), but not stearate (C18: 0), induced tail removal in cercariae. Linoleate stimulated tail loss more strongly than oleate did. Tail loss induced by linoleate was significantly suppressed by incubating cercariae with ethyleneglycol-bis-(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA). Preincubation of cercariae with EGTA for 5 min caused further inhibition of the tail loss. Calcium ionophore A23187 (A23187) increased the cercarial tail-loss rate. When A23187 was combined with linoleate at 0.03 mM, an additive effect on tail loss appeared, whereas the ionophore in combination with linoleate at 0.3 mM had no such effect. EGTA almost completely abolished cercarial tail loss induced by linoleate at both 0.03 and 0.3 mM in the presence and absence of A23187. Linoleate at 3 mM provoked cercarial tail loss even in the presence of EGTA, although the effect of oleate at 3 mM disappeared. Under these conditions, the effect of linoleate was synergistically enhanced by the combination with A23187. A similar, but not significant, synergism took place in cercariae stimulated by oleate. These findings suggest that unsaturated fatty acids enhance calcium influx into cercariae, resulting in triggering tail loss, and, furthermore, that the fatty acids have other potentiating effects on cercarial tail loss. Protein kinases play an insignificant role in fatty acid-induced cercarial tail loss, because a protein kinase C inhibitor, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), and an inhibitor of various protein kinases, staurosporine, had little or no effect on cercarial tail loss induced by linoleate at 3 mM.

Animals↗
PubMed1996

Role of thyroid hormone and retinoid receptors in the homeotic transformation of tails into limbs in frogs.

We provide here further data on the dramatic homeotic transformation of tails into limbs which is induced by retinoids during frog tadpole tail regeneration. The effect can still be produced up to nine days after tail amputation by which time tail regeneration has essentially been completed. Complete tail amputation is needed for the effects to be manifest, partial damage of various sorts to the tail is not enough. We show that as well as retinyl palmitate, other retinoids such as all-trans-retinoic acid and TTNPB, which is a RAR specific retinoid, can induce the homeotic transformation. TTNPB has a 300 x greater potency than retinoic acid. Prolactin, which inhibits thyroid hormone production, prevents the appearance of limbs on the tail from which we conclude that thyroid hormone is needed. We present preliminary evidence from RT-PCR that all six retinoid receptors, the three retinoic acid receptors (RARs), and the three retinoid X receptors (RXRs), are present in the normal tail blastema and that after retinoid treatment RAR alpha, RXR alpha, and RXR beta may be up-regulated. Finally, we show that when RA synthesis is inhibited, normal tail regeneration is inhibited. We conclude that tail regeneration depends upon a particular endogenous level of RA, but that when this level is raised by external administration and thyroid hormone receptors are present the up-regulation of certain retinoid receptors allows novel nuclear receptor interactions which results in the induction of limb-specific genes leading to the appearance of limbs on the tail.

Amputation, Surgical↗
PubMed2003

Phenotype of the neural tube defect mouse model bent tail is not sensitive to maternal folinic acid, myo-inositol, or zinc supplementation.

BACKGROUND: Bent tail is a mouse model for X-linked neural tube defects (NTDs) that is characterized by the presence of exencephaly, a delayed posterior neuropore closure, and a tail phenotype. In addition, Bent tail shows laterality defects and increased prenatal mortality. The congenital malformations of this mouse are caused by a submicroscopic deletion that completely encompasses the gene coding for the zinc finger transcription factor Zic3. In this study we investigated the sensitivity of the phenotype of Bent tail to the nutrients folinic acid, myo-inositol, and zinc. These nutrients are thought to be involved in the etiology of NTDs, in combination with a genetic predisposition. METHODS: The most penetrant phenotype of the Bent tail mouse, the tail malformation, was used as a marker for the nutrient sensitivity of the neural phenotype. The size of the litters and the survival of the offspring, subdivided according to genotype, were analyzed as markers for the nutrient sensitivity of other phenotypic features of Bent tail. RESULTS: In confirmation of earlier studies, we observed the prenatal loss of a number of homozygous females and hemizygous males, as well as the effect of genotype on the tail phenotype of Bent tail. However, periconceptional supplementation of the maternal diet with folinic acid, myo-inositol, or zinc produced no significant effects on either the tail phenotype of the offspring or the size and genotypic composition of the litters. CONCLUSIONS: Bent tail appears to be a folinic acid-, myo-inositol-, and zinc-insensitive mouse model for NTDs.

Animals↗
PubMed1993

Tracing the incorporation of the sperm tail in the mouse zygote and early embryo using an anti-testicular alpha-tubulin antibody.

The mechanism of sperm tail incorporation and the fate of the tail during mouse fertilization and early embryogenesis were examined. Time-lapse video microscopy and anti-tubulin immunofluorescence show that the incorporation of the sperm tail, but not the sperm head, is sensitive to cytochalasin B (a microfilament inhibitor). Colcemid, a microtubule inhibitor, does not affect tail incorporation. High-resolution, low-voltage scanning electron microscopy demonstrates that the plasma membrane covering the sperm tail does not appear to fuse with the oocyte membrane during in vitro fertilization in the presence of cytochalasin. In control and colcemid-treated oocytes, the plasma membrane along the sperm tail, which is oriented tangential to the egg surfaces, appears to fuse with the oocyte membrane at multiple sites. An antibody to testicular alpha-tubulin detects sperm-derived, but not egg, microtubules and this has permitted us to trace the behavior and disappearance of the sperm tail during embryogenesis. Conventional and confocal microscopy show that following sperm incorporation, the tail often splays into multiple fibers. At the two-cell stage, the axoneme may be localized in either blastomere or it may be found to run through the midbody between both blastomeres. The tail appears to shorten by the 8-cell stage and is undetectable after the 16-32 cell stage. In morulae, tail fragments have been found in outer cells but not in inner ones, and fragments have not be found in blastocysts. These data suggest that microtubules of sperm and oocytes contain different isotypes of alpha-tubulin, nongenomic sperm-derived components survive at least to the morula stage of mouse development, and egg microfilaments are involved in the incorporation of the sperm tail but not the sperm head, which demonstrates that motility during sperm incorporation is different in mammals when compared to lower vertebrates and invertebrates.

Actin Cytoskeleton↗
PubMed1993

Different sensitivity to amiloride of body and tail skins of Rana catesbeiana tadpoles during metamorphosis.

Regional differences in potential difference and short-circuit current between the body (dorsal) and the tail skin during metamorphosis of Rana catesbeiana tadpoles were investigated. In body skin, the potential difference and the short-circuit current across the skin develop in two successive steps. At stage XX, the potential difference and the short-circuit current across the body skins were amiloride-insensitive (1st step). At stage XXII, however, amiloride-sensitive potential difference and the short circuit current appeared (2nd step). By contrast, in tail skin the potential difference and the short-circuit current remained amiloride-insensitive (1st step) even at stage XXIII. Since the tail regresses after stage XXIII, the appearance of the second step could not be followed in vivo. To determine whether or not the second step can be induced in the tail, tail skin was cultured under conditions where the skin survives for a much longer period than it does in normally developing tadpoles. Such cultured tail skin generated the amiloride-sensitive potential difference and the short-circuit current and cultured body skin also generated them. Therefore, development of the 2nd step in the tail skin may be delayed in vivo. To characterize the differences between body and tail skin, skins were mutually grafted between body and tail at stage XIII-XV. The body skin grafted on the tail underwent both the 1st and 2nd steps by stage XXII, whereas the tail skin grafted on the body only showed the 1st step by the same stage. These results suggest that the regional specificity of the skin is already established before the prometamorphic stage.

Amiloride↗
PubMed1986

Subunit arrangement of the tail fiber of bacteriophage T3.

A tail fiber of phage T3 is a trimer of the product of gene 17 (gp17). Treatment of T3 phage particles with chymotrypsin resulted in cleavage of only the tail fiber protein, at a site near the distal end of the fiber, causing a decrease of about 10% in the size of gp17 in the treated virion. The N-terminal amino acid sequences of intact and cleaved tail fiber proteins were identical and corresponded to that deduced from the nucleotide sequence of gene 17 except for the absence of the initiation Met residue. These results indicate that cleavage of the tail fiber occurred near the C terminus and suggest that gp17 polypeptides are oriented parallel to each other in the tail fiber. Association of tail fibers with the tail involves the N-terminal region of gp17. Under mild conditions of SDS-polyacrylamide gel electrophoresis, intact tail fibers dissociated from virions but cleaved ones did not. The nucleotide sequences indicate that T3 and T7 gp17 contain many sites that are potentially sensitive to chymotrypsin. In fact, free tail fibers, purified from T3-infected cells, were cleaved to many smaller fragments by chymotrypsin. These results suggest that the attachment of the tail fibers to the tail may induce a change(s) in the configuration and/or arrangement of gp17 to mask the sensitive sites from cleavage by chymotrypsin.

Amino Acid Sequence↗
PubMed1995

Tail bud determination in the vertebrate embryo.

BACKGROUND: Although as humans we lose our tails in the second month of embryonic development, a persistent tail is a prominent structural feature of most adult vertebrates. Indeed, the post-anal tail is part of the definition of a chordate. The internal organization of the developing tail--with neural tube, notochord and paired somites--is the same as that of the main body axis, so it can be expected that the mechanism of tail formation has a close relationship to that of the vertebrate body plan as a whole. Despite this, almost nothing is known about how tails arise. RESULTS: We present evidence to show that the tail bud of Xenopus laevis arises as the result of interactions between distinct zones of tissue at the posterior of the embryo at the neurula stage. These tissue interactions were demonstrated by manipulations of exogastrulae, which normally form no tail, and by transplantation experiments performed on the neural plate of stage 13 neurulae, whereby embryos with supernumary tails were produced. CONCLUSIONS: We propose a new model of tail bud determination, termed the NMC model, to explain the results we have obtained. In this model, the tail bud is initiated by an interaction between two territories in the neural plate and a posterior mesodermal territory.

Animals↗
PubMed2000

A role for epithelial-mesenchymal interactions in tail growth/morphogenesis and chondrogenesis in embryonic mice.

Neurulation involves development from primary germ layers before any differentiation of embryonic mesenchyme. Subsequently, secondary organogenesis is via epithelial-mesenchymal interaction. It is unclear whether formation of the caudal body axis and tail bud in vertebrate embryos is by temporal and causal extension of primary neurulation, by secondary neurulation, or by secondary induction (epithelial-mesenchymal interactions) as seen in organogenesis of the limb buds, kidneys, heart and other embryonic regions. Reports of a ventral ectodermal ridge (VER) associated with tail bud development in rodent embryos imply that tail bud development may share features with limb bud development, in which the apical ectodermal ridge (AER) directs limb bud outgrowth and skeletal patterning. Organ culture or grafting to the chorioallantoic membranes of host chick embryos, of tail bud mesenchyme with or without tail epithelium, demonstrates that both survival and growth of tail mesenchyme depend on the presence of tail epithelium. Initiation of chondrogenesis of tail mesenchyme was similarly dependent on tail epithelium until 10.5 days of gestation, which is when the VER is at its maximal extent. Initiation of myogenesis was independent of the presence of tail epithelium. These results are discussed in relation to the similarity of tail bud to limb bud developed, and to the different mechanisms employed in differentiation of the cranial and caudal ends of vertebrate embryos. Secondary induction of the caudal body region is argued to be fundamental in vertebrate embryogenesis.

Animals↗
PubMed1998

Continuing organizer function during chick tail development.

Development of the posterior body (lumbosacral region and tail) in vertebrates is delayed relative to gastrulation. In amniotes, it proceeds with the replacement of the regressed node and primitive streak by a caudal blastema-like mass of mesenchyme known as the tail bud. Despite apparent morphological dissimilarities, recent results suggest that tail development in amniotes is in essence a continuation of gastrulation, as is the case in Xenopus. However, this has been inferred primarily from the outcome of fate mapping studies demonstrating discrete, regionalized cell populations in the tail bud, like those present at gastrulation. Our analysis of the tail bud distribution of several molecular markers that are expressed in specific spatial domains during chick gastrulation confirms these results. Furthermore, we present evidence that gastrulation-like ingression movements from the surface continue in the early chick tail bud and that the established tail bud retains organizer activity. This 'tail organizer' has the expected properties of being able to recruit uncommitted host cells into a new embryonic axis and induce host neural tissue with posteriorly regionalized gene expression when grafted to competent host cells that are otherwise destined to form only extra-embryonic tissue. Together, these results indicate that chick tail development is mechanistically continuous with gastrulation and that the developing tail in chick may serve as a useful experimental adjunct to investigate the molecular basis of inductive interactions operating during gastrulation, considering that residual tail organizing activity is still present at a surprisingly late stage.

Animals↗
PubMed2004

The coiled tail of the round-headed spermatozoa appears during epididymal passage in GOPC-deficient mice.

Male mice deleting the gene encoding GOPC (Golgi-associated PDZ- and coiled-coil motif-containing protein) are infertile, showing globozoospermia with a coiled tail (Yao et al., 2002). We confirmed how and where tail anomalies were produced in spermatids and epididymal spermatozoa by light and electron microscopy. During spermiogenesis, tail formation occurred normally, but a defect was found at the posterior ring. Thereafter, remarkable sperm tail deformations were induced during epididymal passage. In the proximal caput epidiymidis, the tails remained normal and straight, but most of them coiled around the nucleus in the cauda epididymidis. Coiling is presumed to occur with the migration of the cytoplasmic droplet by the absence of the posterior ring. The connecting piece of the coiled tail was often dislocated or separated from the implantation fossa. Many mitochondria were separated from the outer dense fibers (ODFs) and formed a stratified mitochondrial sheath. Due to this, the distal part of the midpiece became bared of the mitochondrial sheath. The bared ODFs were often bent and disorganized. Tail deformities are attributed to weak or incomplete adhesion between the following structures: 1) plasma membrane and nuclear envelope at the posterior ring, 2) connecting piece and implantation fossa, and 3) mitochondria and ODFs. These defects result in a coiled tail, tail dislocation from the implantation fossa, and the stratified mitochondrial sheath accompanying bared ODFs in the midpiece, respectively. Thus the posterior ring is significant in preventing coiled tail formation. The GOPC-deficient spermatozoa provide a valuable model not only for head but also for tail anomalies.

Adaptor Proteins, Signal Transducing↗
PubMed1991

Morphogenetic features in the tail region of the rat embryo.

The secondary (direct) body formation is a mechanism of development in which morphogenesis of various organs occurs directly from a mass of undifferentiated mesenchymal cells (blastema) without previous formation of germ layers. It is characteristic of the posterior end of the embryonic body, i.e. of the tail bud of tailless and the tail of tailed mammals. Development of the neural tube occurring by this mechanism (secondary neurulation) has been previously explained. We investigated the morphogenetic mechanism by which two other axial structures in the rat tail develop: the tail gut and the notochord. Both structures develop from an axial condensation of undifferentiated mesenchymal cells (tail cord) of tail bud origin. The tail gut forms in a similar way to the secondary neural tube: cells in the ventral part of the tail cord elongate, acquire an apicobasal polarity and form a rosette-like structure around a lumen in the centre. The notochord forms by detachment of a group of cells of the tail cord dorsally to the developing tail gut. The peculiarities of this morphogenetic mechanism in comparison with those in other parts of the embryo are discussed. Causal (including evolutionary) explanations of this mechanism are ruled out.

Animals↗
PubMed1989

[Risks of intravenous injection into the tail of cattle].

Since several years collecting blood from the tail vessels in bovine practice gained a wider range of propagation. Recently veterinarians tried to inject drugs intravenously into the tail vessels of the bovine tail. Therefore we carried out anatomical studies concerning the position of the blood vessels of the bovine tail. 24 tails of slaughtered cattle, which were of different breeds and age (1-4 years old), were examined in respect to the course of their arteries and veins as well on the ventral side. By means of necropsy, frozen cross sections, corrosion anatomy and radiography the position of the tail vessels to each other were compared. In the area of the 2nd to 7th coccygeal vertebra the position of the arteries and veins were being determined. Following results were obtained: 1. The A. cocc. med. runs always ventral in the midline of the tail. 2. The number of ventral veins proximal on the tail varies from 1 to 3. 3. The course of the Vena(ae) cocc. mediana(ae) in the tail region examined is inconstant. The vein lies either left, right, dorsal or ventral of the A. cocc. med. The vein can also cross the area. 4. In 8 of 19 examined cases the V. cocc. med. was closely left to the artery (area of the 5th coccygeal vertebra). After radiologic examination it can be stated that this region can be used for collecting blood of the V. cocc. med. In case of intravenous application of considerable amounts of drugs into the vein of the tail a certain portion can get easily into the closely attached artery and severe complications, as necrosis of the tail can occur. Therefore our clinic recommends generally the use of the Vena jugularis externa for intravenous injection.

Animals↗
PubMed1997

Tail pinch induces fos immunoreactivity within several regions of the male rat brain: effects of age.

Brief, intermittent stressors, such as low-level foot shock or tail pinch, induce a general excitement and autonomic arousal in rats that increases their sensitivity to external incentives. Such stimulation can facilitate a variety of behaviors, including feeding, aggression, sexual activity, parental behavior, and drug taking if the appropriate stimuli exist in the environment. However, the ability of tail pinch to induce general arousal and incentive motivation appears to diminish with age. Here we report on the ability of tail pinch to induce Fos immunoreactivity within several brain regions as a function of age. Young (2-3 months) and middle-aged (12-13 months) male rats were administered either five tail pinches (one every 2 min), one tail pinch, or zero (sham) tail pinches (n = 4 per stimulation condition). Rats were sacrificed 75 min following the onset of stimulation, and their brains were prepared for immunocytochemical detection of Fos protein. Fos immunoreactivity was induced by one and five tail pinches in several brain regions, including the anterior medial preoptic area (mPOA), paraventricular nucleus of the hypothalamus (PVN), paraventricular nucleus of the thalamus (PV-Thal), medial amygdala (MEA), basolateral amygdala (BLA), lateral habenula (LHab), and ventral tegmental area (VTA), of young rats compared with those that received zero tail pinches. In contrast to young rats, middle-aged rats had significantly less Fos induced by one and five tail pinches in the mPOA, PVN, MEA, BLA, and VTA, but an equivalent amount induced in the LHab. Fos immunoreactivity was not found within the medial prefrontal cortex, nucleus accumbens, striatum, lateral septum, or locus coeruleus in either young or old rats. Tail pinch appears to activate regions of the brain known to be involved in behavioral responses to both incentive cues and stressors. The lower level of cellular reactivity to tail pinch in middle-aged rats suggests a diminished neural responsiveness to incentives and stressors.

Aging↗